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You searched for: Journal Biochemistry Remove constraint Journal: Biochemistry Publication Year 2017 Remove constraint Publication Year: 2017 Text Availability Citation in PubAg Remove constraint Text Availability: Citation in PubAg
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1. Activation Mechanism of the Streptomyces Tyrosinase Assisted by the Caddie Protein

Author:
Matoba Yasuyuki; Kihara Shogo; Muraki Yoshimi; Bando Naohiko; Yoshitsu Hironari; Kuroda Teruo; Sakaguchi Miyuki; Kayama Kure’e; Tai Hulin; Hirota Shun; Ogura Takashi; Sugiyama Masanori
Source:
Biochemistry 2017 v.56 no.41 pp. 5593-5603
ISSN:
1520-4995
Subject:
Streptomyces; aerobic conditions; anaerobic conditions; copper; electron paramagnetic resonance spectroscopy; melanogenesis; monophenol monooxygenase; phenol; quinones; reducing agents; spectral analysis; transportation; tyrosine
Abstract:
... Tyrosinase (EC 1.14.18.1), which possesses two copper ions at the active center, catalyzes a rate-limiting reaction of melanogenesis, that is, the conversion of a phenol to the corresponding ortho-quinone. The enzyme from the genus Streptomyces is generated as a complex with a “caddie” protein that assists the transport of two copper ions into the active center. In this complex, the Tyr⁹⁸ residue ...
DOI:
10.1021/acs.biochem.7b00635

2. Activation and Loading of the Starter Unit during Thiocoraline Biosynthesis

Author:
Mori Shogo; Shrestha Sanjib K.; Fernández Javier; Álvarez San Millán María; Garzan Atefeh; Al-Mestarihi Ahmad H.; Lombó Felipe; Garneau-Tsodikova Sylvie
Source:
Biochemistry 2017 v.56 no.34 pp. 4457-4467
ISSN:
1520-4995
Subject:
active sites; acyl carrier protein; adenosine monophosphate; biochemical pathways; biosynthesis; fatty-acid synthase; multigene family; mutants; sequence homology
Abstract:
... The initiation of the nonribosomal peptide synthetase (NRPS) assembly of the bisintercalator natural product thiocoraline involves key enzymatic steps for AMP activation and carrier protein loading of the starter unit 3-hydroxyquinaldic acid (3HQA). Gene cluster data combined with protein sequence homology analysis originally led us to propose that TioJ could be responsible for the AMP activation ...
DOI:
10.1021/acs.biochem.7b00661

3. Activation of Proton Translocation by Respiratory Complex I

Author:
Belevich Nikolai; von Ballmoos Christoph; Verkhovskaya Marina
Source:
Biochemistry 2017 v.56 no.42 pp. 5691-5697
ISSN:
1520-4995
Subject:
NAD (coenzyme); NAD(P)H dehydrogenase (quinone); NADP (coenzyme); adenosinetriphosphatase; ambient temperature; enzyme activity; membrane permeability; protons; quinones
Abstract:
... Activation of proton pumping by reconstituted and native membrane-bound Complex I was studied using optical electric potential- and pH-sensitive probes. We find that reconstituted Complex I has a delay in proton translocation, which is significantly longer than the delay in quinone reductase activity, indicating an initially decoupled state of Complex I. Studies of the amount of NADH required for ...
DOI:
10.1021/acs.biochem.7b00727

4. Activation of the glmS Ribozyme Nucleophile via Overdetermined Hydrogen Bonding

Author:
Bingaman Jamie L.; Gonzalez Inanllely Y.; Wang Bo; Bevilacqua Philip C.
Source:
Biochemistry 2017 v.56 no.33 pp. 4313-4317
ISSN:
1520-4995
Subject:
Lewis bases; acidification; active sites; hydrogen bonding; oxygen; phosphates; ribozymes
Abstract:
... RNA enzymes, or ribozymes, catalyze internal phosphodiester bond cleavage using diverse catalytic strategies. These include the four classic strategies: in-line nucleophilic attack, deprotonation of the 2′-OH nucleophile, protonation of the 5′-O leaving group, and stabilization of developing charge on the nonbridging oxygen atoms of the scissile phosphate. In addition, we recently identified two a ...
DOI:
10.1021/acs.biochem.7b00662

5. Aggregation and Fibril Structure of AβM01–42 and Aβ1–42

Author:
Silvers Robert; Colvin Michael T.; Frederick Kendra K.; Jacavone Angela C.; Lindquist Susan; Linse Sara; Griffin Robert G.
Source:
Biochemistry 2017 v.56 no.36 pp. 4850-4859
ISSN:
1520-4995
Subject:
Alzheimer disease; methionine; neurodegenerative diseases; neurotoxicity; nuclear magnetic resonance spectroscopy; peptides; spectral analysis
Abstract:
... A mechanistic understanding of Aβ aggregation and high-resolution structures of Aβ fibrils and oligomers are vital to elucidating relevant details of neurodegeneration in Alzheimer’s disease, which will facilitate the rational design of diagnostic and therapeutic protocols. The most detailed and reproducible insights into structure and kinetics have been achieved using Aβ peptides produced by reco ...
DOI:
10.1021/acs.biochem.7b00729

6. Analysis of Novel Interactions between Components of the Selenocysteine Biosynthesis Pathway, SEPHS1, SEPHS2, SEPSECS, and SECp43

Author:
Oudouhou Flore; Casu Bastien; Dopgwa Puemi Arnold Steve; Sygusch Jurgen; Baron Christian
Source:
Biochemistry 2017 v.56 no.17 pp. 2261-2270
ISSN:
1520-4995
Subject:
proteins; biosynthesis; Escherichia coli; protein-protein interactions; eukaryotic cells; models; bacteriophages; dimerization; codons; ligases; precipitin tests; selenocysteine; bioluminescence; mammals; energy transfer; X-radiation
Abstract:
... In mammalian cells, the incorporation of the 21st amino acid, selenocysteine, into proteins is guided by the Sec machinery. The function of this protein complex requires several protein–protein and protein–RNA interactions, leading to the incorporation of selenocysteine at UGA codons. It is guided by stem–loop structures localized in the 3′ untranslated regions of the selenoprotein-encoding genes. ...
DOI:
10.1021/acs.biochem.6b01116

7. Analysis of Plasmodium vivax Chloroquine Resistance Transporter Mutant Isoforms

Author:
Hassett Matthew R.; Riegel Bryce E.; Callaghan Paul S.; Roepe Paul D.
Source:
Biochemistry 2017 v.56 no.41 pp. 5615-5622
ISSN:
1520-4995
Subject:
Plasmodium falciparum; Plasmodium vivax; biochemistry; chloroquine; drug resistance; drugs; humans; malaria; mutants; mutation; parasites; quantitative analysis; quinoline; vacuoles
Abstract:
... Chloroquine (CQ) resistance (CQR) in Plasmodium falciparum malaria is widespread and has limited the use of CQ in many regions of the globe. Malaria caused by the related human parasite P. vivax is as widespread as is P. falciparum malaria and has been treated with CQ as extensively as has P. falciparum, suggesting that P. vivax parasites have been selected with CQ as profoundly as have P. falcipa ...
DOI:
10.1021/acs.biochem.7b00749

8. Analyzing the Folding and Binding Steps of an Intrinsically Disordered Protein by Protein Engineering

Author:
Daniela Bonetti; Francesca Troilo; Angelo Toto; Maurizio Brunori; Sonia Longhi; Stefano Gianni
Source:
Biochemistry 2017 v.56 no.29 pp. 3780-3786
ISSN:
1520-4995
Subject:
nucleoproteins; protein folding; phosphoproteins; Measles morbillivirus; amino acid sequences; reaction mechanisms; protein engineering
Abstract:
... Intrinsically disordered proteins (IDPs) are functionally active despite lacking a well-defined three-dimensional structure. Such proteins often undergo a disorder-to-order transition, or induced folding, when binding to their specific physiological partner. Because of cooperativity, the folding and binding steps typically appear as a single event, and therefore, induced folding is extremely diffi ...
DOI:
10.1021/acs.biochem.7b00350

9. Anomeric Selectivity and Product Profile of a Processive Cellulase

Author:
Kari Jeppe; Kont Riin; Borch Kim; Buskov Steen; Olsen Johan Pelck; Cruyz-Bagger Nicolaj; Väljamäe Priit; Westh Peter
Source:
Biochemistry 2017 v.56 no.1 pp. 167-178
ISSN:
1520-4995
Subject:
Trichoderma reesei; binding sites; biomass; carbon cycle; cellobiose; cellulose; endo-1,4-beta-glucanase; enzyme substrates; glucose; hydrolysis; lignocellulose
Abstract:
... Cellobiohydrolases (CBHs) make up an important group of enzymes for both natural carbon cycling and industrial deconstruction of lignocellulosic biomass. The consecutive hydrolysis of one cellulose strand relies on an intricate pattern of enzyme–substrate interactions in the long, tunnel-shaped binding site of the CBH. In this work, we have investigated the initial complexation mode with cellulose ...
DOI:
10.1021/acs.biochem.6b00636

10. Asymmetric Anchoring Is Required for Efficient Ω-Loop Opening and Closing in Cytosolic Phosphoenolpyruvate Carboxykinase

Author:
Cui Danica S.; Broom Aron; Mcleod Matthew J.; Meiering Elizabeth M.; Holyoak Todd
Source:
Biochemistry 2017 v.56 no.15 pp. 2106-2115
ISSN:
1520-4995
Subject:
cytosol; mutants; phosphoenolpyruvate carboxykinase (GTP); structure-activity relationships
Abstract:
... Mobile Ω-loops play essential roles in the function of many enzymes. Here we investigated the importance of a residue lying outside of the mobile Ω-loop element in the catalytic function of an H477R variant of cytosolic phosphoenolpyruvate carboxykinase using crystallographic, kinetic, and computational analysis. The crystallographic data suggest that the efficient transition of the Ω-loop to the ...
DOI:
10.1021/acs.biochem.7b00178

11. Atomistic Molecular Dynamics Simulations of Mitochondrial DNA Polymerase γ: Novel Mechanisms of Function and Pathogenesis

Author:
Euro Liliya; Haapanen Outi; Róg Tomasz; Vattulainen Ilpo; Suomalainen Anu; Sharma Vivek
Source:
Biochemistry 2017 v.56 no.9 pp. 1227-1238
ISSN:
1520-4995
Subject:
DNA replication; DNA-directed DNA polymerase; active sites; catalytic activity; crystal structure; humans; mitochondrial DNA; molecular dynamics; mutation; neurodegenerative diseases; pathogenesis; patients
Abstract:
... DNA polymerase γ (Pol γ) is a key component of the mitochondrial DNA replisome and an important cause of neurological diseases. Despite the availability of its crystal structures, the molecular mechanism of DNA replication, the switch between polymerase and exonuclease activities, the site of replisomal interactions, and functional effects of patient mutations that do not affect direct catalysis h ...
DOI:
10.1021/acs.biochem.6b00934

12. Autoantigen La Regulates MicroRNA Processing from Stem–Loop Precursors by Association with DGCR8

Author:
Zheng Quan; Yang Hai-Jie; Yuan Y. Adam
Source:
Biochemistry 2017 v.56 no.46 pp. 6098-6110
ISSN:
1520-4995
Subject:
binding capacity; humans; microRNA; oligonucleotides
Abstract:
... In humans, primary microRNA (pri-miRNA) processing starts from precise cleavage of the stem loop, which is catalyzed by the Drosha–DGCR8 complex. However, the significant inconsistencies in the expression levels among primary, precursor, and mature miRNAs clearly indicate that many other factors may be involved in this regulation. Here, we utilize a newly developed RNA affinity technique to isolat ...
DOI:
10.1021/acs.biochem.7b00693

13. Berberine Induces Toxicity in HeLa Cells through Perturbation of Microtubule Polymerization by Binding to Tubulin at a Unique Site

Author:
Raghav Darpan; Ashraf Shabeeba M.; Mohan Lakshmi; Rathinasamy Krishnan
Source:
Biochemistry 2017 v.56 no.20 pp. 2594-2611
ISSN:
1520-4995
Subject:
Fourier transform infrared spectroscopy; antineoplastic activity; antineoplastic agents; berberine; binding sites; brain; clinical trials; colchicine; depolymerization; energy transfer; flow cytometry; fluorescence; fluorescence microscopy; goats; in vitro studies; inhibitory concentration 50; interphase; microtubules; mitosis; molecular dynamics; paclitaxel; polymerization; toxicity; tryptophan; tubulin
Abstract:
... Berberine has been used traditionally for its diverse pharmacological actions. It exhibits remarkable anticancer activities and is currently under clinical trials. In this study, we report that the anticancer activity of berberine could be partly due to its inhibitory actions on tubulin and microtubule assembly. Berberine inhibited the proliferation of HeLa cells with an IC₅₀ of 18 μM and induced ...
DOI:
10.1021/acs.biochem.7b00101

14. The Binding Mode of N-Hydroxyamidines to Indoleamine 2,3-Dioxygenase 1 (IDO1)

Author:
Röhrig Ute F.; Zoete Vincent; Michielin Olivier
Source:
Biochemistry 2017 v.56 no.33 pp. 4323-4325
ISSN:
1520-4995
Subject:
X-radiation; heme; immunotherapy; indoleamine 2,3-dioxygenase; iron; ligands; neoplasms; nitrogen; oxygen; pharmacology; quantum mechanics
Abstract:
... Indoleamine 2,3-dioxygenase 1 (IDO1) is an important target in cancer immunotherapy. The most advanced clinical compound, epacadostat (INCB024360), binds to the heme cofactor of IDO1 through an N-hydroxyamidine function. Conflicting binding modes have recently been proposed, reporting iron binding either through the hydroxyamidine oxygen or through the hydroxyamidine nitrogen atom. Here, we use qu ...
DOI:
10.1021/acs.biochem.7b00586

15. Binding and Energetics of Electron Transfer between an Artificial Four-Helix Mn-Protein and Reaction Centers from Rhodobacter sphaeroides

Author:
Espiritu Eduardo; Olson Tien L.; Williams JoAnn C.; Allen James P.
Source:
Biochemistry 2017 v.56 no.49 pp. 6460-6469
ISSN:
1520-4995
Subject:
Gibbs free energy; Rhodobacter sphaeroides; amino acid substitution; bacteriochlorophyll; cytochromes; dissociation; electron transfer; lighting; manganese; oxidation; pH; photosynthetic reaction centers; spectroscopy
Abstract:
... The ability of an artificial four-helix bundle Mn-protein, P1, to bind and transfer an electron to photosynthetic reaction centers from the purple bacterium Rhodobacter sphaeroides was characterized using optical spectroscopy. Upon illumination of reaction centers, an electron is transferred from P, the bacteriochlorophyll dimer, to QA, the primary electron acceptor. The P1 Mn-protein can bind to ...
DOI:
10.1021/acs.biochem.7b00978

16. Binding of Copper and Cisplatin to Atox1 Is Mediated by Glutathione through the Formation of Metal–Sulfur Clusters

Author:
Dolgova Natalia V.; Yu Corey; Cvitkovic John P.; Hodak Miroslav; Nienaber Kurt H.; Summers Kelly L.; Cotelesage Julien J. H.; Bernholc Jerzy; Kaminski George A.; Pickering Ingrid J.; George Graham N.; Dmitriev Oleg Y.
Source:
Biochemistry 2017 v.56 no.24 pp. 3129-3141
ISSN:
1520-4995
Subject:
cisplatin; copper; drug therapy; free radicals; glutathione; metabolism; molecular weight; neoplasms; polymers; toxicity; transporters
Abstract:
... Copper is an essential nutrient required for many biological processes involved in primary metabolism, but free copper is toxic due to its ability to catalyze formation of free radicals. To prevent toxic effects, in the cell copper is bound to proteins and low molecular weight compounds, such as glutathione, at all times. The widely used chemotherapy agent cisplatin is known to bind to copper-tran ...
DOI:
10.1021/acs.biochem.7b00293

17. Binding of Thioflavin-T to Amyloid Fibrils Leads to Fluorescence Self-Quenching and Fibril Compaction

Author:
Lindberg David J.; Wenger Anna; Sundin Elin; Wesén Emelie; Westerlund Fredrik; Esbjörner Elin K.
Source:
Biochemistry 2017 v.56 no.16 pp. 2170-2174
ISSN:
1520-4995
Subject:
amyloid; emissions factor; fluorescence; fluorescence emission spectroscopy; in vitro studies; insulin
Abstract:
... Thioflavin-T binds to and detects amyloid fibrils via fluorescence enhancement. Using a combination of linear dichroism and fluorescence spectroscopies, we report that the relation between the emission intensity and binding of thioflavin-T to insulin fibrils is nonlinear and discuss this in relation to its use in kinetic assays. We demonstrate, from fluorescence lifetime recordings, that the nonli ...
DOI:
10.1021/acs.biochem.7b00035

18. Biocatalysis of a Paclitaxel Analogue: Conversion of Baccatin III to N-Debenzoyl-N-(2-furoyl)paclitaxel and Characterization of an Amino Phenylpropanoyl CoA Transferase

Author:
Chelsea K. Thornburg; Tyler Walter; Kevin D. Walker
Source:
Biochemistry 2017 v.56 no.44 pp. 5920-5930
ISSN:
1520-4995
Subject:
Taxus; acyltransferases; antineoplastic agents; binding proteins; biocatalysis; biochemical pathways; catalysts; cytotoxicity; kinetics; macrophages; maltose; paclitaxel; regioselectivity
Abstract:
... In this study, we demonstrate an enzyme cascade reaction using a benzoate CoA ligase (BadA), a modified nonribosomal peptide synthase (PheAT), a phenylpropanoyltransferase (BAPT), and a benzoyltransferase (NDTNBT) to produce an anticancer paclitaxel analogue and its precursor from the commercially available biosynthetic intermediate baccatin III. BAPT and NDTNBT are acyltransferases on the biosynt ...
DOI:
10.1021/acs.biochem.7b00912

19. Biological Roles of Protein Kinetic Stability

Author:
Colón Wilfredo; Church Jennifer; Sen Jayeeta; Thibeault Jane; Trasatti Hannah; Xia Ke
Source:
Biochemistry 2017 v.56 no.47 pp. 6179-6186
ISSN:
1520-4995
Subject:
activation energy; half life; phenotype; protective effect; proteins; proteolysis
Abstract:
... A protein’s stability may range from nonexistent, as in the case of intrinsically disordered proteins, to very high, as indicated by a protein’s resistance to degradation, even under relatively harsh conditions. The stability of this latter group is usually under kinetic control because of a high activation energy for unfolding that virtually traps the protein in a specific conformation, thereby c ...
DOI:
10.1021/acs.biochem.7b00942

20. Can Reduction of NO to N2O in Cytochrome c Dependent Nitric Oxide Reductase Proceed through a Trans-Mechanism?

Author:
Blomberg Margareta R. A.
Source:
Biochemistry 2017 v.56 no.1 pp. 120-131
ISSN:
1520-4995
Subject:
active sites; chemical bonding; cytochrome c; denitrification; electron paramagnetic resonance spectroscopy; energy; heme iron; ions; nitric oxide; nitric oxide reductase (cytochrome c); nitrogen; nitrous oxide
Abstract:
... As part of microbial denitrification, NO is reduced to N₂O in the membrane bound enzyme nitric oxide reductase, NOR. The N–N coupling occurs in the diiron binuclear active site, BNC, and different mechanisms for this reaction step have been suggested. Computational studies have supported a so-called cis:b₃-mechanism, in which the hyponitrite product of the reductive N–N bond formation coordinates ...
DOI:
10.1021/acs.biochem.6b00788

21. A Carbocyclic Curcumin Inhibits Proliferation of Gram-Positive Bacteria by Targeting FtsZ

Author:
Groundwater Paul W.; Narlawar Rajeshwar; Liao Vivian Wan Yu; Bhattacharya Anusri; Srivastava Shalini; Kunal Kishore; Doddareddy Munikumar; Oza Pratik M.; Mamidi Ramesh; Marrs Emma C. L.; Perry John D.; Hibbs David E.; Panda Dulal
Source:
Biochemistry 2017 v.56 no.3 pp. 514-524
ISSN:
1520-4995
Subject:
Bacillus subtilis; Gram-positive bacteria; antibacterial properties; antibiotic resistance; cell division; cell proliferation; confocal microscopy; curcumin; dissociation; fluorescent antibody technique; guanosinetriphosphatase; humans; image analysis; membrane potential; methicillin; methicillin-resistant Staphylococcus aureus; minimum inhibitory concentration; neoplasm cells; tubulin; uterine cervical neoplasms
Abstract:
... Inhibition of FtsZ assembly has been found to stall bacterial cell division. Here, we report the identification of a potent carbocyclic curcumin analogue (2d) that inhibits Bacillus subtilis 168 cell proliferation by targeting the assembly of FtsZ. 2d also showed potent inhibitory activity (minimum inhibitory concentrations of 2–4 mg/L) against several clinically important species of Gram-positive ...
DOI:
10.1021/acs.biochem.6b00879

22. The Catalase Activity of Catalase-Peroxidases Is Modulated by Changes in the pKa of the Distal Histidine

Author:
Machuqueiro Miguel; Victor Bruno; Switala Jacek; Villanueva Jacylyn; Rovira Carme; Fita Ignacio; Loewen Peter C.
Source:
Biochemistry 2017 v.56 no.17 pp. 2271-2281
ISSN:
1520-4995
Subject:
catalase; crosslinking; enzyme activity; heme; heme iron; histidine; pH
Abstract:
... The unusual Met-Tyr-Trp adduct composed of cross-linked side chains along with an associated mobile Arg is essential for catalase activity in catalase-peroxidases. In addition, acidic residues in the entrance channel, in particular an Asp and a Glu ∼7 and ∼15 Å, respectively, from the heme, significantly enhance catalase activity. The mechanism by which these channel carboxylates influence catalas ...
DOI:
10.1021/acs.biochem.6b01276

23. Caught before Released: Structural Mapping of the Reaction Trajectory for the Sofosbuvir Activating Enzyme, Human Histidine Triad Nucleotide Binding Protein 1 (hHint1)

Author:
Rachit Shah; Kimberly M. Maize; Xin Zhou; Barry C. Finzel; Carston R. Wagner
Source:
Biochemistry 2017 v.56 no.28 pp. 3559-3570
ISSN:
1520-4995
Subject:
Lewis bases; active sites; binding proteins; catalytic activity; crystallography; drugs; enzyme substrates; enzymes; hepatitis C; histidine; humans; hydrolysis; nucleosides; protons
Abstract:
... Human histidine triad nucleotide binding protein 1 (hHint1) is classified as an efficient nucleoside phosphoramidase and acyl-adenosine monophosphate hydrolase. Human Hint1 has been shown to be essential for the metabolic activation of nucleotide antiviral pronucleotides (i.e., proTides), such as the FDA approved hepatitis C drug, sofosbuvir. The active site of hHint1 comprises an ensemble of stri ...
DOI:
10.1021/acs.biochem.7b00148

24. Caulobacter crescentus Cell Cycle-Regulated DNA Methyltransferase Uses a Novel Mechanism for Substrate Recognition

Author:
Clayton B. Woodcock; Aziz B. Yakubov; Norbert O. Reich
Source:
Biochemistry 2017 v.56 no.30 pp. 3913-3922
ISSN:
1520-4995
Subject:
Caulobacter crescentus; DNA; DNA methylation; RNA; cell cycle; cell differentiation; epigenetics; methyltransferases; transcription factors
Abstract:
... Caulobacter crescentus relies on DNA methylation by the cell cycle-regulated methyltransferase (CcrM) in addition to key transcription factors to control the cell cycle and direct cellular differentiation. CcrM is shown here to efficiently methylate its cognate recognition site 5′-GANTC-3′ in single-stranded and hemimethylated double-stranded DNA. We report the Kₘ, kcₐₜ, kₘₑₜₕyₗₐₜᵢₒₙ, and Kd for s ...
DOI:
10.1021/acs.biochem.7b00378

25. Chaperone-like Activity of Calnuc Prevents Amyloid Aggregation

Author:
Kanuru Madhavi; Aradhyam Gopala Krishna
Source:
Biochemistry 2017 v.56 no.1 pp. 149-159
ISSN:
1520-4995
Subject:
Alzheimer disease; Parkinson disease; alcohol dehydrogenase; amyloid; calreticulin; catalase; cell culture; chlorides; enzyme activity; guanidinium; heat stress; human diseases; insulin; luciferase; lysozyme; malate dehydrogenase; noninsulin-dependent diabetes mellitus; prion diseases; protein unfolding; sequence homology; spectrin; toxicity; urea
Abstract:
... Calnuc is a ubiquitously expressed protein of the EF-hand Ca²⁺-binding superfamily. Previous studies have implicated it in Ca²⁺-sensitive physiological processes, whereas details of its function and involvement in human diseases are lacking. Drawing upon the sequence homology of calnuc with calreticulin, we propose it functions as a molecular chaperone-like protein. In cells under thermal, chemica ...
DOI:
10.1021/acs.biochem.6b00660

26. Characterization of Blebbistatin Inhibition of Smooth Muscle Myosin and Nonmuscle Myosin-2

Author:
Zhang Hai-Man; Ji Huan-Hong; Ni Tong; Ma Rong-Na; Wang Aibing; Li Xiang-dong
Source:
Biochemistry 2017 v.56 no.32 pp. 4235-4243
ISSN:
1520-4995
Subject:
inhibitory concentration 50; mutagenesis; mutants; myosin; smooth muscle; striated muscle
Abstract:
... Blebbistatin is a potent and specific inhibitor of the motor functions of class II myosins, including striated muscle myosin and nonmuscle myosin-2 (NM2). However, the blebbistatin inhibition of NM2c has not been assessed and remains controversial with respect to its efficacy with smooth muscle myosin (SmM), which is highly homologous to NM2. To clarify these issues, we analyzed the effects of ble ...
DOI:
10.1021/acs.biochem.7b00311

27. Characterization of DNA Binding by the Isolated N-Terminal Domain of Vaccinia Virus DNA Topoisomerase IB

Author:
Reed Benjamin; Yakovleva Lyudmila; Shuman Stewart; Ghose Ranajeet
Source:
Biochemistry 2017 v.56 no.26 pp. 3307-3317
ISSN:
1520-4995
Subject:
DNA; DNA topoisomerase; Vaccinia virus; active sites; amino acids; calorimetry; crystal structure; hydrodynamics; ionic strength; mutation; nuclear magnetic resonance spectroscopy; nucleotide sequences; titration; transesterification
Abstract:
... Vaccinia TopIB (vTopIB), a 314-amino acid eukaryal-type IB topoisomerase, recognizes and transesterifies at the DNA sequence 5′-(T/C)CCTT↓, leading to the formation of a covalent DNA–(3′-phosphotyrosyl²⁷⁴)–enzyme intermediate in the supercoil relaxation reaction. The C-terminal segment of vTopIB (amino acids 81–314), which engages the DNA minor groove at the scissile phosphodiester, comprises an a ...
DOI:
10.1021/acs.biochem.7b00042

28. Characterization of G4–G4 Crosstalk in the c-KIT Promoter Region

Author:
Rigo Riccardo; Sissi Claudia
Source:
Biochemistry 2017 v.56 no.33 pp. 4309-4312
ISSN:
1520-4995
Subject:
DNA; electrophoresis; nucleotides; promoter regions; spectroscopy; surface plasmon resonance; therapeutics
Abstract:
... The proximal promoter of c-KIT contains a peculiar domain that consists of three short G-rich sequences that are close together and can fold into noncanonical DNA secondary structures called G-quadruplexes (G4). Here, we focused on a sequence containing two consecutive G4 (kit2 and kit*). By electrophoretic, surface plasmon resonance, and spectroscopic techniques, we demonstrated that they retain ...
DOI:
10.1021/acs.biochem.7b00660

29. Characterization of Heme Orientational Disorder in a Myoglobin Reconstituted with a Trifluoromethyl-Group-Substituted Heme Cofactor

Author:
Kanai Yuki; Harada Ayaka; Shibata Tomokazu; Nishimura Ryu; Namiki Kosuke; Watanabe Miho; Nakamura Shunpei; Yumoto Fumiaki; Senda Toshiya; Suzuki Akihiro; Neya Saburo; Yamamoto Yasuhiko
Source:
Biochemistry 2017 v.56 no.34 pp. 4500-4508
ISSN:
1520-4995
Subject:
Physeter macrocephalus; crystal structure; heme; mutation; myoglobin; nuclear magnetic resonance spectroscopy; thermodynamics
Abstract:
... The orientation of a CF₃-substituted heme in sperm whale myoglobin and L29F, H64L, L29F/H64Q, and H64Q variant proteins has been investigated using ¹⁹F NMR spectroscopy to elucidate structural factors responsible for the thermodynamic stability of the heme orientational disorder, i.e., the presence of two heme orientations differing by a 180° rotation about the 5–15 meso axis, with respect to the ...
DOI:
10.1021/acs.biochem.7b00457

30. Characterization of Hsp90 Co-Chaperone p23 Cleavage by Caspase-7 Uncovers a Peptidase–Substrate Interaction Involving Intrinsically Disordered Regions

Author:
Martini Cyrielle; Bédard Mikaël; Lavigne Pierre; Denault Jean-Bernard
Source:
Biochemistry 2017 v.56 no.38 pp. 5099-5111
ISSN:
1520-4995
Subject:
NAD ADP-ribosyltransferase; apoptosis; bioinformatics; caspase-3; caspase-7; catalytic activity; chimerism; inflammation; mutagenesis; proteins; proteolysis; structure-activity relationships
Abstract:
... Caspases are cysteinyl peptidases involved in inflammation and apoptosis during which hundreds of proteins are cleaved by executioner caspase-3 and -7. Despite the fact that caspase-3 has a higher catalytic activity, caspase-7 is more proficient at cleaving poly(ADP ribose) polymerase 1 (PARP1) because it uses an exosite within its N-terminal domain (NTD). Here, we demonstrate that molecular deter ...
DOI:
10.1021/acs.biochem.7b00298

31. Characterization of a UGT84 Family Glycosyltransferase Provides New Insights into Substrate Binding and Reactivity of Galloylglucose Ester-Forming UGTs

Author:
Wilson Alexander E.; Feng Xiaoxue; Ono Nadia N.; Holland Doron; Amir Rachel; Tian Li
Source:
Biochemistry 2017 v.56 no.48 pp. 6389-6400
ISSN:
1520-4995
Subject:
amino acids; animal and human health; engineering; esters; gallic acid; genistein; glycosylation; glycosyltransferases; kinetics; metabolites; models; sequence analysis; site-directed mutagenesis; structure-activity relationships; sugars
Abstract:
... Galloylated plant specialized metabolites play important roles in plant–environment interactions and in the promotion of human and animal health. The galloylation reactions are mediated by the formation of galloylglucose esters from gallic acid and UDP-glucose, catalyzed by the plant UGT84 family glycosyltransferases. To explore and exploit the structural determinants of UGT84 activities, we perfo ...
DOI:
10.1021/acs.biochem.7b00946

32. Characterizations of the Interactions between Escherichia coli Periplasmic Chaperone HdeA and Its Native Substrates during Acid Stress

Author:
Yu Xing-Chi; Yang Chengfeng; Ding Jienv; Niu Xiaogang; Hu Yunfei; Jin Changwen
Source:
Biochemistry 2017 v.56 no.43 pp. 5748-5757
ISSN:
1520-4995
Subject:
Escherichia coli; acid tolerance; acidification; dissociation; hydrophobicity; models; nuclear magnetic resonance spectroscopy; pH; proteins
Abstract:
... The bacterial acid-resistant chaperone HdeA is a “conditionally disordered” protein that functions at low pH when it undergoes a transition from a well-folded dimer to an unfolded monomer. The dimer dissociation and unfolding processes result in exposure of hydrophobic surfaces that allows binding to a broad range of client proteins. To fully elucidate the chaperone mechanism of HdeA, it is crucia ...
DOI:
10.1021/acs.biochem.7b00724

33. Charges in Hydrophobic Environments: A Strategy for Identifying Alternative States in Proteins

Author:
Robinson Aaron C.; Majumdar Ananya; Schlessman Jamie L.; García-Moreno E Bertrand
Source:
Biochemistry 2017 v.56 no.1 pp. 212-218
ISSN:
1520-4995
Subject:
algorithms; crystal structure; hydrophobicity; micrococcal nuclease; nuclear magnetic resonance spectroscopy; pH; proteins
Abstract:
... In the V23E variant of staphylococcal nuclease, Glu-23 has a pKₐ of 7.5. At low pH, Glu-23 is neutral and buried in the hydrophobic interior of the protein. Crystal structures and NMR spectroscopy experiments show that when Glu-23 becomes charged, the protein switches into an open state in which strands β1 and β2 separate from the β-barrel; the remaining structure is unaffected. In the open state ...
DOI:
10.1021/acs.biochem.6b00843

34. Chemical Denaturants Smoothen Ruggedness on the Free Energy Landscape of Protein Folding

Author:
Malhotra Pooja; Jethva Prashant N.; Udgaonkar Jayant B.
Source:
Biochemistry 2017 v.56 no.31 pp. 4053-4063
ISSN:
1520-4995
Subject:
Gibbs free energy; biochemistry; energy; mass spectrometry; mutants; mutation; protein folding; roughness
Abstract:
... To characterize experimentally the ruggedness of the free energy landscape of protein folding is challenging, because the distributed small free energy barriers are usually dominated by one, or a few, large activation free energy barriers. This study delineates changes in the roughness of the free energy landscape by making use of the observation that a decrease in ruggedness is accompanied invari ...
DOI:
10.1021/acs.biochem.7b00367

35. Chemical Editing of Macrocyclic Natural Products and Kinetic Profiling Reveal Slow, Tight-Binding Histone Deacetylase Inhibitors with Picomolar Affinities

Author:
Kitir Betül; Maolanon Alex R.; Ohm Ragnhild G.; Colaço Ana R.; Fristrup Peter; Madsen Andreas S.; Olsen Christian A.
Source:
Biochemistry 2017 v.56 no.38 pp. 5134-5146
ISSN:
1520-4995
Subject:
binding capacity; chemical elements; drugs; epigenetics; histone deacetylase; medicine; metabolism; neoplasms; synthesis
Abstract:
... Histone deacetylases (HDACs) are validated targets for treatment of certain cancer types and play numerous regulatory roles in biology, ranging from epigenetics to metabolism. Small molecules are highly important as tool compounds for probing these mechanisms as well as for the development of new medicines. Therefore, detailed mechanistic information and precise characterization of the chemical pr ...
DOI:
10.1021/acs.biochem.7b00725

36. Chemical Synthesis Demonstrates That Dynamic O-Glycosylation Regulates the Folding and Functional Conformation of a Pivotal EGF12 Domain of the Human NOTCH1 Receptor

Author:
Hayakawa Shun; Yokoi Yasuhiro; Hinou Hiroshi; Nishimura Shin-Ichiro
Source:
Biochemistry 2017 v.56 no.33 pp. 4379-4391
ISSN:
1520-4995
Subject:
calcium; cell differentiation; endoplasmic reticulum; humans; ligands; neoplasms; nuclear magnetic resonance spectroscopy; post-translational modification; signal transduction; synthesis; trisaccharides
Abstract:
... The interaction of the human NOTCH1 receptor and its ligands is a crucial step in initiating the intracellular signal transductions, in which O-glycosylation of the extracellular EGF-like domain strongly affects multiple aspects of cell differentiation, development, and cancer biology. However, consequences of biosynthetic O-glycosylation processes in the endoplasmic reticulum (ER) and Golgi on th ...
DOI:
10.1021/acs.biochem.7b00372

37. Chemistry Is Dead. Long Live Chemistry!

Author:
Lavis Luke D.
Source:
Biochemistry 2017 v.56 no.39 pp. 5165-5170
ISSN:
1520-4995
Subject:
chemistry; fluorescence microscopy; fluorescent dyes; fluorescent proteins; image analysis; protein engineering
Abstract:
... Chemistry, once king of fluorescence microscopy, was usurped by the field of fluorescent proteins. The increased demands of modern microscopy techniques on the “photon budget” require better and brighter fluorophores, causing a renewed interest in synthetic dyes. Here, we review the recent advances in biochemistry, protein engineering, and organic synthesis that have allowed a triumphant return of ...
DOI:
10.1021/acs.biochem.7b00529

38. Chiral Ramachandran Plots I: Glycine

Author:
Baruch-Shpigler Yael; Wang Huan; Tuvi-Arad Inbal; Avnir David
Source:
Biochemistry 2017 v.56 no.42 pp. 5635-5643
ISSN:
1520-4995
Subject:
amino acids; optical isomerism; polypeptides; protein structure; proteins
Abstract:
... Ramachandran plots (RPs) map the wealth of conformations of the polypeptide backbone and are widely used to characterize protein structures. A limitation of the RPs is that they are based solely on two dihedral angles for each amino acid residue and provide therefore only a partial picture of the conformational richness of the protein. Here we extend the structural RP analysis of proteins from a t ...
DOI:
10.1021/acs.biochem.7b00525

39. Chlorinated Glycopeptide Antibiotic Peptide Precursors Improve Cytochrome P450-Catalyzed Cyclization Cascade Efficiency

Author:
Peschke Madeleine; Brieke Clara; Goode Rob J. A.; Schittenhelm Ralf B.; Cryle Max J.
Source:
Biochemistry 2017 v.56 no.9 pp. 1239-1247
ISSN:
1520-4995
Subject:
Oxya; active sites; antibiotics; chlorination; chlorine; crosslinking; enzymes; glycopeptides
Abstract:
... The activity of glycopeptide antibiotics (GPAs) depends upon important structural modifications to their precursor heptapeptide backbone: specifically, the cytochrome P450-catalyzed oxidative cross-linking of aromatic side chains as well as the halogenation of specific residues within the peptide. The timing of halogenation and its effect on the cyclization of the peptide are currently unclear. Ou ...
DOI:
10.1021/acs.biochem.6b01102

40. Chromophore Isomer Stabilization Is Critical to the Efficient Fluorescence of Cyan Fluorescent Proteins

Author:
Gotthard Guillaume; von Stetten David; Clavel Damien; Noirclerc-Savoye Marjolaine; Royant Antoine
Source:
Biochemistry 2017 v.56 no.49 pp. 6418-6422
ISSN:
1520-4995
Subject:
fluorescence; green fluorescent protein; irradiation; isomers; mutagenesis; pH; photobleaching; protein engineering
Abstract:
... ECFP, the first usable cyan fluorescent protein (CFP), was obtained by adapting the tyrosine-based chromophore environment in green fluorescent protein to that of a tryptophan-based one. This first-generation CFP was superseded by the popular Cerulean, CyPet, and SCFP3A that were engineered by rational and random mutagenesis, yet the latter CFPs still exhibit suboptimal properties of pH sensitivit ...
DOI:
10.1021/acs.biochem.7b01088

41. Cold Adaptation of Triosephosphate Isomerase

Author:
Åqvist Johan
Source:
Biochemistry 2017 v.56 no.32 pp. 4169-4176
ISSN:
1520-4995
Subject:
Gibbs free energy; Moritella marina; cold; enthalpy; freezing point; molecular dynamics; mutation; psychrophilic bacteria; temperature; thermal stability; triose-phosphate isomerase; yeasts
Abstract:
... The main problem for enzymes from psychrophilic species, which need to work near the freezing point of liquid water, is the exponential decay of reaction rates as the temperature is decreased. Cold-adapted enzymes have solved this problem by shifting the activation enthalpy–entropy balance for the catalyzed reaction compared to those of their mesophilic orthologs. To understand the structural basi ...
DOI:
10.1021/acs.biochem.7b00523

42. Cold Denaturation of the HIV-1 Protease Monomer

Author:
Rösner Heike I.; Caldarini Martina; Prestel Andreas; Vanoni Maria A.; Broglia Ricardo A.; Aliverti Alessandro; Tiana Guido; Kragelund Birthe B.
Source:
Biochemistry 2017 v.56 no.8 pp. 1029-1032
ISSN:
1520-4995
Subject:
Human immunodeficiency virus 1; denaturation; hydrodynamics; nuclear magnetic resonance spectroscopy; proteinases; temperature
Abstract:
... The human immunodeficiency virus-1 (HIV-1) protease is a complex protein that in its active form adopts a homodimer dominated by β-sheet structures. We have discovered a cold-denatured state of the monomeric subunit of HIV-1 protease that is populated above 0 °C and therefore directly accessible to various spectroscopic approaches. Using nuclear magnetic resonance secondary chemical shifts, temper ...
DOI:
10.1021/acs.biochem.6b01141

43. Combining H/D Exchange Mass Spectrometry and Computational Docking To Derive the Structure of Protein–Protein Complexes

Author:
Roberts Victoria A.; Pique Michael E.; Hsu Simon; Li Sheng
Source:
Biochemistry 2017 v.56 no.48 pp. 6329-6342
ISSN:
1520-4995
Subject:
DNA repair; amides; deuterium; energy; humans; mass spectrometry; models; protein structure; protein-protein interactions; solvents; uracil-DNA glycosylase
Abstract:
... Protein–protein interactions are essential for biological function, but structures of protein–protein complexes are difficult to obtain experimentally. To derive the protein complex of the DNA-repair enzyme human uracil-DNA-glycosylase (hUNG) with its protein inhibitor (UGI), we combined rigid-body computational docking with hydrogen/deuterium exchange mass spectrometry (DXMS). Computational docki ...
DOI:
10.1021/acs.biochem.7b00643

44. Comparative Analysis Reveals Furoyl in Vivo Selective Hydroxyl Acylation Analyzed by Primer Extension Reagents Form Stable Ribosyl Ester Adducts

Author:
Chan Dalen; Feng Chao; Zhen Yuran; Flynn Ryan A.; Spitale Robert C.
Source:
Biochemistry 2017 v.56 no.13 pp. 1811-1814
ISSN:
1520-4995
Subject:
dithiothreitol; reverse transcription; acylation; hydrolysis; Lewis acids; temperature; RNA
Abstract:
... RNA molecules depend on structural elements that are critical for cellular function. Chemical methods for probing RNA structure have emerged as a necessary component of characterizing RNA function. As such, understanding the limitations and idiosyncrasies of these methods is essential for their utility. Selective hydroxyl acylation has emerged as a common method for analyzing RNA structure. Ester ...
DOI:
10.1021/acs.biochem.7b00128

45. Complex Stability During the Transport Cycle of a Subclass I ECF Transporter

Author:
Finkenwirth Friedrich; Kirsch Franziska; Eitinger Thomas
Source:
Biochemistry 2017 v.56 no.34 pp. 4578-4583
ISSN:
1520-4995
Subject:
adenosine triphosphate; biotin; detergents; hydrolysis; prokaryotic cells; solutes; transporters
Abstract:
... The mechanism of energy-coupling factor (ECF) transporters, a special type of ATP-binding-cassette importers for micronutrients in prokaryotes, is a matter of controversial discussion. Among subclass II ECF transporters, a single ECF interacts with several substrate-binding integral membrane proteins (S units) for individual solutes. Release and catch of the S unit, previously observed experimenta ...
DOI:
10.1021/acs.biochem.7b00390

46. Computational Prediction and Design for Creating Iteratively Larger Heterospecific Coiled Coil Sets

Author:
Crooks Richard O.; Lathbridge Alexander; Panek Anna S.; Mason Jody M.
Source:
Biochemistry 2017 v.56 no.11 pp. 1573-1584
ISSN:
1520-4995
Subject:
circular dichroism spectroscopy; computer software; data collection; denaturation; electrostatic interactions; gel chromatography; peptides; prediction; protein-protein interactions; synthetic biology
Abstract:
... A major biochemical goal is the ability to mimic nature in engineering highly specific protein–protein interactions (PPIs). We previously devised a computational interactome screen to identify eight peptides that form four heterospecific dimers despite 32 potential off-targets. To expand the speed and utility of our approach and the PPI toolkit, we have developed new software to derive much larger ...
DOI:
10.1021/acs.biochem.7b00047

47. The Conformation of the Epidermal Growth Factor Receptor Transmembrane Domain Dimer Dynamically Adapts to the Local Membrane Environment

Author:
Bocharov Eduard V.; Bragin Pavel E.; Pavlov Konstantin V.; Bocharova Olga V.; Mineev Konstantin S.; Polyansky Anton A.; Volynsky Pavel E.; Efremov Roman G.; Arseniev Alexander S.
Source:
Biochemistry 2017 v.56 no.12 pp. 1697-1705
ISSN:
1520-4995
Subject:
dimerization; epidermal growth factor receptors; humans; lipids; micelles; molecular dynamics; nuclear magnetic resonance spectroscopy; pathological processes and conditions; signal transduction
Abstract:
... The epidermal growth factor receptor (EGFR) family is an important class of receptor tyrosine kinases, mediating a variety of cellular responses in normal biological processes and in pathological states of multicellular organisms. Different modes of dimerization of the human EGFR transmembrane domain (TMD) in different membrane mimetics recently prompted us to propose a novel signal transduction m ...
DOI:
10.1021/acs.biochem.6b01085

48. The Conformational Change in Elongation Factor Tu Involves Separation of Its Domains

Author:
Jonathan Lai; Zhaleh Ghaemi; Zaida Luthey-Schulten
Source:
Biochemistry 2017 v.56 no.45 pp. 5972-5979
ISSN:
1520-4995
Subject:
Gibbs free energy; aminoacyl transfer RNA; guanosine triphosphate; guanosinetriphosphatase; hydrolysis; ribosomes; sequence homology; translation (genetics)
Abstract:
... Elongation factor Tu (EF-Tu) is a highly conserved GTPase that is responsible for supplying the aminoacylated tRNA to the ribosome. Upon binding to the ribosome, EF-Tu undergoes GTP hydrolysis, which drives a major conformational change, triggering the release of aminoacylated tRNA to the ribosome. Using a combination of molecular simulation techniques, we studied the transition between the pre- a ...
DOI:
10.1021/acs.biochem.7b00591

49. Conformational Dynamics of the Lipopolysaccharide from Escherichia coli O91 Revealed by Nuclear Magnetic Resonance Spectroscopy and Molecular Simulations

Author:
Pilar Blasco; Dhilon S. Patel; Olof Engström; Wonpil Im; Göran Widmalm
Source:
Biochemistry 2017 v.56 no.29 pp. 3826-3839
ISSN:
1520-4995
Subject:
Gibbs free energy; Gram-negative bacteria; O-antigens; calcium; carbon; cations; enterohemorrhagic Escherichia coli; molecular dynamics; nuclear magnetic resonance spectroscopy; potassium; serotypes; stable isotopes; sugars
Abstract:
... The outer leaflet of the outer membrane in Gram-negative bacteria contains lipopolysaccharides (LPS) as a major component, and the outer membrane provides a physical barrier and protection against hostile environments. The enterohemorrhagic Escherichia coli of serogroup O91 has an O-antigen polysaccharide (PS) with five sugar residues in the repeating unit (RU), and the herein studied O-antigen PS ...
DOI:
10.1021/acs.biochem.7b00106

50. Conformational Heterogeneity and DNA Recognition by the Morphogen Bicoid

Author:
Adhikary Ramkrishna; Tan Yun Xuan; Liu Jian; Zimmermann Jörg; Holcomb Matthew; Yvellez Carolyn; Dawson Philip E.; Romesberg Floyd E.
Source:
Biochemistry 2017 v.56 no.22 pp. 2787-2793
ISSN:
1520-4995
Subject:
DNA; Drosophila; RNA; absorption; denaturation; homeodomain proteins; nucleotide sequences; transcription factors
Abstract:
... The morphogenic activity of the Drosophila transcription factor bicoid (Bcd), the first morphogenic protein identified, is controlled by its DNA binding homeodomain. Homeodomains mediate developmental processes in all multicellular organisms, but the Bcd homeodomain appears to be unique as it can bind multiple DNA sequences and even RNA. All homeodomain proteins adopt a three-helix fold, with resi ...
DOI:
10.1021/acs.biochem.7b00255

51. Conformational Heterogeneity in a Fully Complementary DNA Three-Way Junction with a GC-Rich Branchpoint

Author:
Toulmin Anita; Baltierra-Jasso Laura E.; Morten Michael J.; Sabir Tara; McGlynn Peter; Schröder Gunnar F.; Smith Brian O.; Magennis Steven W.
Source:
Biochemistry 2017 v.56 no.37 pp. 4985-4991
ISSN:
1520-4995
Subject:
complementary DNA; energy transfer; fluorescence emission spectroscopy; molecular models; nanomaterials; nuclear magnetic resonance spectroscopy
Abstract:
... DNA three-way junctions (3WJs) are branched structures that serve as important biological intermediates and as components in DNA nanostructures. We recently derived the global structure of a fully complementary 3WJ and found that it contained unpaired bases at the branchpoint, which is consistent with previous observations of branch flexibility and branchpoint reactivity. By combining high-resolut ...
DOI:
10.1021/acs.biochem.7b00677

52. A Cooperative Folding Unit as the Structural Link for Energetic Coupling within a Protein

Author:
Nathan W. Gardner; Sarah M. McGinness; Jainik Panchal; Elizabeth M. Topp; Chiwook Park
Source:
Biochemistry 2017 v.56 no.50 pp. 6555-6564
ISSN:
1520-4995
Subject:
Escherichia coli; active sites; dimerization; ligands; mass spectrometry; metabolites; mutation; solvents
Abstract:
... Previously, we demonstrated that binding of a ligand to Escherichia coli cofactor-dependent phosphoglycerate mutase (dPGM), a homodimeric protein, is energetically coupled with dimerization. The equilibrium unfolding of dPGM occurs with a stable, monomeric intermediate. Binding of several nonsubstrate metabolites stabilizes the dimeric native form over the monomeric intermediate, reducing the popu ...
DOI:
10.1021/acs.biochem.7b00850

53. Cooperative Interactions in the Hammerhead Ribozyme Drive pKa Shifting of G12 and Its Stacked Base C17

Author:
Frankel Erica A.; Strulson Christopher A.; Keating Christine D.; Bevilacqua Philip C.
Source:
Biochemistry 2017 v.56 no.20 pp. 2537-2548
ISSN:
1520-4995
Subject:
guanosine; models; Hepatitis delta virus; guanine; magnesium; pH; ribozymes; catalytic activity; metal ions
Abstract:
... General acid–base catalysis is a key mechanistic strategy in protein and RNA enzymes. Ribozymes use hydrated metal ions, nucleobases, and organic cofactors to carry this out. In most small ribozymes, a guanosine is positioned to participate in proton transfer with the nucleophilic 2′-OH. The unshifted pKₐ values for nucleobases and solvated metal ions are far from neutrality, however, and thus non ...
DOI:
10.1021/acs.biochem.7b00174

54. Covalent Allosteric Inactivation of Protein Tyrosine Phosphatase 1B (PTP1B) by an Inhibitor–Electrophile Conjugate

Author:
Punthasee Puminan; Laciak Adrian R.; Cummings Andrea H.; Ruddraraju Kasi Viswanatharaju; Lewis Sarah M.; Hillebrand Roman; Singh Harkewal; Tanner John J.; Gates Kent S.
Source:
Biochemistry 2017 v.56 no.14 pp. 2051-2060
ISSN:
1520-4995
Subject:
active sites; drugs; enzyme inactivation; mass spectrometry; protein-tyrosine-phosphatase
Abstract:
... Protein tyrosine phosphatase 1B (PTP1B) is a validated drug target, but it has proven difficult to develop medicinally useful, reversible inhibitors of this enzyme. Here we explored covalent strategies for the inactivation of PTP1B using a conjugate composed of an active site-directed 5-aryl-1,2,5-thiadiazolidin-3-one 1,1-dioxide inhibitor connected via a short linker to an electrophilic α-bromoac ...
DOI:
10.1021/acs.biochem.7b00151

55. A Critical Role of Ser26 Hydrogen Bonding in Aβ42 Assembly and Toxicity

Author:
Roychaudhuri Robin; Huynh Tien-Phat V.; Whitaker Taylor R.; Hodara Elisabeth; Condron Margaret M.; Teplow David B.
Source:
Biochemistry 2017 v.56 no.48 pp. 6321-6324
ISSN:
1520-4995
Subject:
Alzheimer disease; amyloid; cytotoxicity; hydrogen bonding; hydrophobicity; moieties; peptides; structure-activity relationships
Abstract:
... Amyloid β-protein (Aβ) assembly is a seminal process in Alzheimer’s disease. Elucidating the mechanistic features of this process is thought to be vital for the design and targeting of therapeutic agents. Computational studies of the most pathologic form of Aβ, the 42-residue Aβ42 peptide, have suggested that hydrogen bonding involving Ser26 may be particularly important in organizing a monomer fo ...
DOI:
10.1021/acs.biochem.7b00772

56. Crystal Structure and Characterization of Novel Human Histone H3 Variants, H3.6, H3.7, and H3.8

Author:
Taguchi Hiroyuki; Xie Yan; Horikoshi Naoki; Maehara Kazumitsu; Harada Akihito; Nogami Jumpei; Sato Koichi; Arimura Yasuhiro; Osakabe Akihisa; Kujirai Tomoya; Iwasaki Takeshi; Semba Yuichiro; Tachibana Taro; Kimura Hiroshi; Ohkawa Yasuyuki; Kurumizaka Hitoshi
Source:
Biochemistry 2017 v.56 no.16 pp. 2184-2196
ISSN:
1520-4995
Subject:
DNA; amino acids; crystal structure; epigenetics; histones; humans; hydrophobic bonding; mutational analysis; nucleosomes; pseudogenes; thermal stability
Abstract:
... Non-allelic histone variants are considered as epigenetic factors that regulate genomic DNA functions in eukaryotic chromosomes. In this study, we identified three new human histone H3 variants (named H3.6, H3.7, and H3.8), which were previously annotated as pseudogenes. H3.6 and H3.8 conserve the H3.3-specific amino acid residues, but H3.7 shares the specific amino acid residues with H3.1. We suc ...
DOI:
10.1021/acs.biochem.6b01098

57. The Crystal Structure of a Maxi/Mini-Ferritin Chimera Reveals Guiding Principles for the Assembly of Protein Cages

Author:
Thomas A. Cornell; Yogesh Srivastava; Ralf Jauch; Rongli Fan; Brendan P. Orner
Source:
Biochemistry 2017 v.56 no.30 pp. 3894-3899
ISSN:
1520-4995
Subject:
capsid; crystal structure; drugs; ferritin; homeostasis; iron; models; nanomaterials; protein quaternary structure; viruses
Abstract:
... Cage proteins assemble into nanoscale structures with large central cavities. They play roles, including those as virus capsids and chaperones, and have been applied to drug delivery and nanomaterials. Furthermore, protein cages have been used as model systems to understand and design protein quaternary structure. Ferritins are ubiquitous protein cages that manage iron homeostasis and oxidative da ...
DOI:
10.1021/acs.biochem.7b00312

58. Cyclotide Structure and Function: The Role of Membrane Binding and Permeation

Author:
Troeira Henriques Sónia; Craik David J.
Source:
Biochemistry 2017 v.56 no.5 pp. 669-682
ISSN:
1520-4995
Subject:
bioactive properties; cyclic peptides; drugs; phosphatidylethanolamines; physicochemical properties; trypsin inhibitors
Abstract:
... There is growing interest in the use of peptides as therapeutic drugs and, in particular, in the potential of cyclotides, a family of cyclic peptides with remarkable stability and amenability to sequence engineering, as scaffolds in drug design. As well as having an ultrastable structure, many natural cyclotides have intrinsic biological activities with potential pharmaceutical or agricultural app ...
DOI:
10.1021/acs.biochem.6b01212

59. Cytoskeletal-like Filaments of Ca2+-Calmodulin-Dependent Protein Kinase II Are Formed in a Regulated and Zn2+-Dependent Manner

Author:
Hoffman Laurel; Li Lin; Alexov Emil; Sanabria Hugo; Waxham M. Neal
Source:
Biochemistry 2017 v.56 no.15 pp. 2149-2160
ISSN:
1520-4995
Subject:
amino acids; binding sites; cadmium; calcium; calcium-calmodulin-dependent protein kinase; calmodulin; cations; chelating agents; cobalt; copper; crystal structure; cytoskeletal proteins; magnesium; models; neurons; nickel; zinc
Abstract:
... Ca²⁺-calmodulin-dependent protein kinase II (CaMKII) is highly abundant in neurons, where its concentration reaches that typically found for cytoskeletal proteins. Functional reasons for such a high concentration are not known, but given the multitude of known binding partners for CaMKII, a role as a scaffolding molecule has been proposed. In this report, we provide experimental evidence that demo ...
DOI:
10.1021/acs.biochem.7b00028

60. Deciphering Nature’s Intricate Way of N,S-Dimethylating l-Cysteine: Sequential Action of Two Bifunctional Adenylation Domains

Author:
Mori Shogo; Garzan Atefeh; Tsodikov Oleg V.; Garneau-Tsodikova Sylvie
Source:
Biochemistry 2017 v.56 no.46 pp. 6087-6097
ISSN:
1520-4995
Subject:
amino acids; biosynthesis; methyltransferases
Abstract:
... Dimethylation of amino acids consists of an interesting and puzzling series of events that could be achieved, during nonribosomal peptide biosynthesis, either by a single adenylation (A) domain interrupted by a methyltransferase (M) domain or by the sequential action of two of such independent enzymes. Herein, to establish the method by which Nature N,S-dimethylates l-Cys, we studied its formation ...
DOI:
10.1021/acs.biochem.7b00980

61. Decoding of O-Linked Glycosylation by Mass Spectrometry

Author:
Mulagapati SriHariRaju; Koppolu Veerendra; Raju T. Shantha
Source:
Biochemistry 2017 v.56 no.9 pp. 1218-1226
ISSN:
1520-4995
Subject:
chemical bonding; desorption; dissociation; electron transfer; glycomics; glycopeptides; glycoproteins; glycosylation; ionization; mass spectrometry; polysaccharides; protein structure
Abstract:
... Protein glycosylation (N- and O-linked) plays an important role in many biological processes, including protein structure and function. However, the structural elucidation of glycans, specifically O-linked glycans, remains a major challenge and is often overlooked during protein analysis. Recently, mass spectrometry (MS) has matured as a powerful technology for high-quality analytical characteriza ...
DOI:
10.1021/acs.biochem.6b01244

62. Defective Ribonucleoproteins, Mistakes in RNA Processing, and Diseases

Author:
Mihailovic Mia K.; Chen Angela; Gonzalez-Rivera Juan C.; Contreras Lydia M.
Source:
Biochemistry 2017 v.56 no.10 pp. 1367-1382
ISSN:
1520-4995
Subject:
RNA; neoplasms; neurodegenerative diseases; ribonucleoproteins
Abstract:
... Ribonucleoproteins (RNPs) are vital to many cellular events. To this end, many neurodegenerative diseases and cancers have been linked to RNP malfunction, particularly as this relates to defective processing of cellular RNA. The connection of RNPs and diseases has also propagated a shift of focus onto RNA targeting from traditional protein targeting treatments. However, therapeutic development in ...
DOI:
10.1021/acs.biochem.6b01134

63. Defining Molecular Details of the Chemistry of Biofilm Formation by Raman Microspectroscopy

Author:
Carey Paul R.; Gibson Blake R.; Gibson Jordan F.; Greenberg Michael E.; Heidari-Torkabadi Hossein; Pusztai-Carey Marianne; Weaver Sean T.; Whitmer Grant R.
Source:
Biochemistry 2017 v.56 no.17 pp. 2247-2250
ISSN:
1520-4995
Subject:
Escherichia coli; RNA; Raman spectroscopy; Staphylococcus epidermidis; aluminum foil; biofilm; carbohydrate content; developmental stages; freeze drying; gentian violet; photography; plankton; staining; water vapor
Abstract:
... Two protocols that allow for the comparison of Raman spectra of planktonic cells and biofilm formed from these cells in their growth phase have been developed. Planktonic cells are washed and flash-frozen in <1 min to reduce the time for metabolic changes during processing, prior to freeze-drying. Biofilm is formed by standing cells in 50 μL indentations in aluminum foil in an atmosphere of satura ...
DOI:
10.1021/acs.biochem.7b00116

64. Design, Synthesis, and Experimental Validation of Peptide Ligands Targeting Mycobacterium tuberculosis σ Factors

Author:
Vishwanath Sneha; Banerjee Sunaina; Jamithireddy Anil K.; Srinivasan Narayanaswamy; Gopal Balasubramanian; Chatterjee Jayanta
Source:
Biochemistry 2017 v.56 no.16 pp. 2209-2218
ISSN:
1520-4995
Subject:
DNA-directed RNA polymerase; Mycobacterium tuberculosis; bacteria; drugs; gene expression; host-pathogen relationships; interferometry; ligands; peptide libraries; prokaryotic cells; sigma factors
Abstract:
... Transcription in prokaryotes is a multistep process and is primarily regulated at the initiation stage. σ factors are involved in promoter recognition and thus govern prokaryotic gene expression. Mycobacterium tuberculosis (Mtb) σ factors have been previously suggested as important drug targets through large-scale genome analyses. Here we demonstrate the feasibility of specific targeting of Mtb σ ...
DOI:
10.1021/acs.biochem.6b01267

65. Design, Synthesis, and Potency of Pyruvate Dehydrogenase Complex E1 Inhibitors against Cyanobacteria

Author:
Zhou Yuan; Feng Jiangtao; He Hongwu; Hou Leifeng; Jiang Wen; Xie Dan; Feng Lingling; Cai Meng; Peng Hao
Source:
Biochemistry 2017 v.56 no.49 pp. 6491-6502
ISSN:
1520-4995
Subject:
Escherichia coli; Microcystis; Synechocystis sp. PCC 6803; active sites; algae; copper; copper sulfate; correlation; hydrogen bonding; inhibitory concentration 50; median effective concentration; molecular models; pyruvate dehydrogenase (lipoamide); site-directed mutagenesis
Abstract:
... Safe and effective algaecides are needed to control agriculturally and environmentally significant algal species. Four series (6, 10, 17, and 21) of 29 novel 4-aminopyrimidine derivatives were rationally designed and synthesized. A part of 10, 17, and 21 displayed potent inhibition of Escherichia coli pyruvate dehydrogenase complex E1 (E. coli PDHc-E1) (IC₅₀ = 2.12–18.06 μM) and good inhibition of ...
DOI:
10.1021/acs.biochem.7b00636

66. Detection of a Subset of Posttranscriptional Transfer RNA Modifications in Vivo with a Restriction Fragment Length Polymorphism-Based Method

Author:
Wulff Thomas F.; Argüello Rafael J.; Molina Jordàn Marc; Roura Frigolé Helena; Hauquier Glenn; Filonava Liudmila; Camacho Noelia; Gatti Evelina; Pierre Philippe; Ribas de Pouplana Lluís; Torres Adrian G.
Source:
Biochemistry 2017 v.56 no.31 pp. 4029-4038
ISSN:
1520-4995
Subject:
restriction fragment length polymorphism; adenosine; messenger RNA; DNA damage; guanosine; deamination; restriction endonucleases; reverse transcriptase polymerase chain reaction; enzymatic treatment; gene expression; human physiology; reverse transcription; transfer RNA
Abstract:
... Transfer RNAs (tRNAs) are among the most heavily modified RNA species. Posttranscriptional tRNA modifications (ptRMs) play fundamental roles in modulating tRNA structure and function and are being increasingly linked to human physiology and disease. Detection of ptRMs is often challenging, expensive, and laborious. Restriction fragment length polymorphism (RFLP) analyses study the patterns of DNA ...
DOI:
10.1021/acs.biochem.7b00324

67. Developing a Fluorescent Toolbox To Shed Light on the Mysteries of RNA

Author:
Alexander Seth C.; Devaraj Neal K.
Source:
Biochemistry 2017 v.56 no.39 pp. 5185-5193
ISSN:
1520-4995
Subject:
RNA; RNA-binding proteins; fluorescence; image analysis; in situ hybridization; oligonucleotides
Abstract:
... Technologies that detect and image RNA have illuminated the complex roles played by RNA, redefining the traditional and superficial role first outlined by the central dogma of biology. Because there is such a wide diversity of RNA structure arising from an assortment of functions within biology, a toolbox of approaches have emerged for investigation of this important class of biomolecules. These m ...
DOI:
10.1021/acs.biochem.7b00510

68. Differential Effects of Strand Asymmetry on the Energetics and Structural Flexibility of DNA Internal Loops

Author:
Tran Thao; Cannon Brian
Source:
Biochemistry 2017 v.56 no.49 pp. 6448-6459
ISSN:
1520-4995
Subject:
DNA; asymmetry; energy transfer; fluorescence; melting; models; nanomaterials; nucleotides; thermodynamics
Abstract:
... Internal loops within structured nucleic acids disrupt local base stacking and destabilize neighboring helical domains; however, these structural motifs also expand the conformational and functional capabilities of structured nucleic acids. Variations in the size, distribution of loop nucleotides on opposing strands (strand asymmetry), and sequence alter their biophysical properties. Here, the the ...
DOI:
10.1021/acs.biochem.7b00930

69. Differential Ligand Binding Specificities of the Pulmonary Collectins Are Determined by the Conformational Freedom of a Surface Loop

Author:
Rynkiewicz Michael J.; Wu Huixing; Cafarella Tanya R.; Nikolaidis Nikolaos M.; Head James F.; Seaton Barbara A.; McCormack Francis X.
Source:
Biochemistry 2017 v.56 no.31 pp. 4095-4105
ISSN:
1520-4995
Subject:
binding capacity; binding sites; calcium; carbohydrate binding; innate immunity; inositols; lectins; ligands; lipid A; mutants; mutation; pathogen-associated molecular patterns; phenotype; surfactants
Abstract:
... Lung surfactant proteins (SPs) play critical roles in surfactant function and innate immunity. SP-A and SP-D, members of the collectin family of C-type lectins, exhibit distinct ligand specificities, effects on surfactant structure, and host defense functions despite extensive structural homology. SP-A binds to dipalmitoylphosphatidylcholine (DPPC), the major surfactant lipid component, but not ph ...
DOI:
10.1021/acs.biochem.6b01313

70. Direct Measurement of Trafficking of the Cystic Fibrosis Transmembrane Conductance Regulator to the Cell Surface and Binding to a Chemical Chaperone

Author:
Zhang Zhihui; Baksh Michael M.; Finn M. G.; Heidary David K.; Richards Christopher I.
Source:
Biochemistry 2017 v.56 no.1 pp. 240-249
ISSN:
1520-4995
Subject:
binding sites; cystic fibrosis; interferometry; mutation; plasma membrane; synergism; temperature
Abstract:
... Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) result in the disease cystic fibrosis. Deletion of Phe508, the most prevalent mutation associated with this disease, disrupts trafficking of the protein. Small molecule correctors yield moderate improvements in the trafficking of ΔF508-CFTR to the plasma membrane. It is currently not known if correctors increase the level ...
DOI:
10.1021/acs.biochem.6b00853

71. Discovery of Inactive Conformation-Selective Kinase Inhibitors by Utilizing Cascade Assays

Author:
Wang Weixue; Krosky Daniel; Ahn Kay
Source:
Biochemistry 2017 v.56 no.34 pp. 4449-4456
ISSN:
1520-4995
Subject:
biochemistry; drugs; guidelines; humans; mathematical models
Abstract:
... Achieving selectivity across the human kinome is a major hurdle in kinase inhibitor drug discovery. Targeting inactive (vs active) kinase conformations offers advantages in achieving selectivity because of their more diversified structures. Discovery of inactive conformation-selective inhibitors, however, has been hampered partly by the lack of general assay methods. Herein, we show that such inhi ...
DOI:
10.1021/acs.biochem.7b00521

72. The Disordered Linker in p53 Participates in Nonspecific Binding to and One-Dimensional Sliding along DNA Revealed by Single-Molecule Fluorescence Measurements

Author:
Subekti Dwiky Rendra Graha; Murata Agato; Itoh Yuji; Fukuchi Satoshi; Takahashi Hiroto; Kanbayashi Saori; Takahashi Satoshi; Kamagata Kiyoto
Source:
Biochemistry 2017 v.56 no.32 pp. 4134-4144
ISSN:
1520-4995
Subject:
DNA; fluorescence; mutation; neutralization; transcription factors
Abstract:
... The tumor suppressor p53 is a multidomain transcription factor that can quickly bind to its target DNA by sliding along the DNA strand. We hypothesized that the intrinsically disordered and positively charged linker of p53 regulates its search dynamics first by directly interacting with DNA and second by modulating hopping of the core domain. To test the two hypotheses, we prepared five variants o ...
DOI:
10.1021/acs.biochem.7b00292

73. A Dry Transition State More Compact Than the Native State Is Stabilized by Non-Native Interactions during the Unfolding of a Small Protein

Author:
Sreemantee Sen; Rama Reddy Goluguri; Jayant B. Udgaonkar
Source:
Biochemistry 2017 v.56 no.29 pp. 3699-3703
ISSN:
1520-4995
Subject:
hydrophobicity; mixing; mutants; mutation; protein folding; proteins
Abstract:
... Defining the role of non-native interactions in directing the course of protein folding or unfolding reactions has been a difficult challenge. In particular, the extent to which such interactions play a productive role by stabilizing the structures of transition states (TSs) found on the folding and unfolding pathways of proteins is not known. On the contrary, it is thought that the TSs are expand ...
DOI:
10.1021/acs.biochem.7b00388

74. Dual Lifetimes for Complexes between Glutathione-S-transferase (hGSTA1-1) and Product-like Ligands Detected by Single-Molecule Fluorescence Imaging

Author:
Pettersson John R.; Lanni Frederick; Rule Gordon S.
Source:
Biochemistry 2017 v.56 no.31 pp. 4073-4083
ISSN:
1520-4995
Subject:
active sites; energy transfer; fluorescence; glutathione transferase; humans; image analysis; ligands; models; point mutation
Abstract:
... Single-molecule fluorescence techniques were used to characterize the binding of products and inhibitors to human glutathione S-transferase A1-1 (hGSTA1-1). The identification of at least two different bound states for the wild-type enzyme suggests that there are at least two conformations of the protein, consistent with the model that ligand binding promotes closure of the carboxy-terminal helix ...
DOI:
10.1021/acs.biochem.7b00030

75. Dynamic and Energetic Signatures of Adenine Tracts in a rA-dT RNA-DNA Hybrid and in Homologous RNA-DNA, RNA-RNA, and DNA-DNA Double Helices

Author:
Huang Yuegao; Russu Irina M.
Source:
Biochemistry 2017 v.56 no.19 pp. 2446-2454
ISSN:
1520-4995
Subject:
adenine; ammonia; hybrids; nuclear magnetic resonance spectroscopy; nucleic acids; nucleotide sequences; protons
Abstract:
... Nuclear magnetic resonance spectroscopy and proton exchange are being used to characterize the opening reactions of individual base pairs in the RNA-DNA hybrid 5′-rGCGAUAAAAAGGCC-3′/5′-dGGCCTTTTTATCGC-3′. The hybrid contains a central tract of five rA-dT base pairs. The rates and the equilibrium constant of the opening reaction for each base pair are determined from the dependence of the exchange ...
DOI:
10.1021/acs.biochem.6b01122

76. Dynamics of Aromatic Side Chains in the Active Site of FKBP12

Author:
Weininger Ulrich; Modig Kristofer; Geitner Anne-Juliane; Schmidpeter Philipp A. M.; Koch Johanna R.; Akke Mikael
Source:
Biochemistry 2017 v.56 no.1 pp. 334-343
ISSN:
1520-4995
Subject:
active sites; calcium; catalytic activity; humans; hydrogen bonding; immune response; isomerization; nuclear magnetic resonance spectroscopy; protein folding; signal transduction
Abstract:
... FKBP12, a small human enzyme, aids protein folding by catalyzing cis–trans isomerization of peptidyl-prolyl bonds, and is involved in cell signaling pathways, calcium regulation, and the immune response. The underlying molecular mechanisms are not fully understood, but it is well-known that aromatic residues in the active site and neighboring loops are important for substrate binding and catalysis ...
DOI:
10.1021/acs.biochem.6b01157

77. Dynamics of Lysine as a Heme Axial Ligand: NMR Analysis of the Chlamydomonas reinhardtii Hemoglobin THB1

Author:
Preimesberger Matthew R.; Majumdar Ananya; Lecomte Juliette T. J.
Source:
Biochemistry 2017 v.56 no.4 pp. 551-569
ISSN:
1520-4995
Subject:
Chlamydomonas reinhardtii; electron transfer; energy; heme; heme iron; hemoglobin; histidine; ligands; lysine; metabolism; nitrates; nitric oxide; nuclear magnetic resonance spectroscopy; oxidation; pH; solvents; temperature
Abstract:
... Nitrate metabolism in Chlamydomonas reinhardtii involves THB1, a monomeric hemoglobin thought to function as a nitric oxide dioxygenase (NOD). NOD activity requires dioxygen and nitric oxide binding followed by a one-electron oxidation of the heme iron and nitrate release. Unlike pentacoordinate flavohemoglobins, which are efficient NODs, THB1 uses two iron axial ligands: the conserved proximal hi ...
DOI:
10.1021/acs.biochem.6b00926

78. Effect of N-Terminal Myristoylation on the Active Conformation of Gαi1–GTP

Author:
van Keulen Siri C.; Rothlisberger Ursula
Source:
Biochemistry 2017 v.56 no.1 pp. 271-280
ISSN:
1520-4995
Subject:
G-protein coupled receptors; G-proteins; cell membranes; lipids; molecular dynamics; myristoylation; physiological transport; protein-protein interactions; signal transduction
Abstract:
... G proteins are part of the G-protein-coupled receptor (GPCR) signal transduction cascade in which they transfer a signal from the membrane-embedded GPCR to other proteins in the cell. In the case of the inhibitory G-protein heterotrimer, permanent N-terminal myristoylation can transiently localize the Gαᵢ subunit at the membrane as well as crucially influence Gαᵢ’s function in the GTP-bound confor ...
DOI:
10.1021/acs.biochem.6b00388

79. Effect of the Flexible Regions of the Oncoprotein Mouse Double Minute X on Inhibitor Binding Affinity

Author:
Lingyun Qin; Huili Liu; Rong Chen; Jingjing Zhou; Xiyao Cheng; Yao Chen; Yongqi Huang; Zhengding Su
Source:
Biochemistry 2017 v.56 no.44 pp. 5943-5954
ISSN:
1520-4995
Subject:
amino acid sequences; binding capacity; chemical interactions; drugs; engineering; ligands; mice; models; molecular dynamics; mutants; oncogene proteins; pharmacology; prediction; protein conformation; protein engineering; screening
Abstract:
... The oncoprotein MdmX (mouse double minute X) is highly homologous to Mdm2 (mouse double minute 2) in terms of their amino acid sequences and three-dimensional conformations, but Mdm2 inhibitors exhibit very weak affinity for MdmX, providing an excellent model for exploring how protein conformation distinguishes and alters inhibitor binding. The intrinsic conformation flexibility of proteins plays ...
DOI:
10.1021/acs.biochem.7b00903

80. Effects of Catalytic Action and Ligand Binding on Conformational Ensembles of Adenylate Kinase

Author:
Onuk Emre; Badger John; Wang Yu Jing; Bardhan Jaydeep; Chishti Yasmin; Akcakaya Murat; Brooks Dana H.; Erdogmus Deniz; Minh David D. L.; Makowski Lee
Source:
Biochemistry 2017 v.56 no.34 pp. 4559-4567
ISSN:
1520-4995
Subject:
Escherichia coli; X-radiation; adenosine diphosphate; adenosine monophosphate; adenosine triphosphate; adenylate kinase; cluster analysis; crystal structure; ligands; models
Abstract:
... Crystal structures of adenylate kinase (AdK) from Escherichia coli capture two states: an “open” conformation (apo) obtained in the absence of ligands and a “closed” conformation in which ligands are bound. Other AdK crystal structures suggest intermediate conformations that may lie on the transition pathway between these two states. To characterize the transition from open to closed states in sol ...
DOI:
10.1021/acs.biochem.7b00351

81. Effects of Doxorubicin, Cisplatin, and Tamoxifen on the Metabolic Profile of Human Breast Cancer MCF-7 Cells As Determined by 1H High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance

Author:
Maria Roberta M.; Altei Wanessa F.; Selistre-de-Araujo Heloisa S.; Colnago Luiz A.
Source:
Biochemistry 2017 v.56 no.16 pp. 2219-2224
ISSN:
1520-4995
Subject:
acetates; betaine; biomarkers; breast neoplasms; choline; cisplatin; doxorubicin; drug therapy; fatty acids; humans; metabolism; metabolites; nuclear magnetic resonance spectroscopy; proteins; qualitative analysis; tamoxifen; taurine
Abstract:
... Doxorubicin (Doxo), cisplatin (Cis), and tamoxifen (Tamo) are part of many chemotherapeutic regimens. However, there have been limited studies of the way metabolism in breast cancer is affected by chemotherapy. We studied, through ¹H high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy, the metabolic profile of human breast cancer MCF-7 control (Con) cells as w ...
DOI:
10.1021/acs.biochem.7b00015

82. Efficient and Flexible Preparation of Biosynthetic Microperoxidases

Author:
Kleingardner Erin C.; Asher Wesley B.; Bren Kara L.
Source:
Biochemistry 2017 v.56 no.1 pp. 143-148
ISSN:
1520-4995
Subject:
Vibrio cholerae; active sites; agarose; biosynthesis; catalysts; cysteine proteinases; heme; heme proteins; inositols; leucine; models; peptides; proteolysis
Abstract:
... Heme peptides and their derivatives, also called microperoxidases (MPs), are employed as heme protein active site models, catalysts, and charge-transfer chromophores. In this work, two approaches to the biosynthesis of novel MPs are described. In one method, heme peptides are expressed as C-terminal tags to the protein azurin and the MP is liberated by proteolytic cleavage by an endopeptidase. In ...
DOI:
10.1021/acs.biochem.6b00915

83. The Electron Bifurcating FixABCX Protein Complex from Azotobacter vinelandii: Generation of Low-Potential Reducing Equivalents for Nitrogenase Catalysis

Author:
Ledbetter Rhesa N.; Garcia Costas Amaya M.; Lubner Carolyn E.; Mulder David W.; Tokmina-Lukaszewska Monika; Artz Jacob H.; Patterson Angela; Magnuson Timothy S.; Jay Zackary J.; Duan H. Diessel; Miller Jacquelyn; Plunkett Mary H.; Hoben John P.; Barney Brett M.; Carlson Ross P.; Miller Anne-Frances; Bothner Brian; King Paul W.; Peters John W.; Seefeldt Lance C.
Source:
Biochemistry 2017 v.56 no.32 pp. 4177-4190
ISSN:
1520-4995
Subject:
Azotobacter vinelandii; NAD (coenzyme); adenosine triphosphate; ammonia; catalytic activity; crosslinking; electron paramagnetic resonance spectroscopy; electron transfer; electrons; genes; mass spectrometry; metabolism; microorganisms; models; nitrogen; nitrogenase; oxidation; reducing agents; thermodynamics; ubiquinones
Abstract:
... The biological reduction of dinitrogen (N₂) to ammonia (NH₃) by nitrogenase is an energetically demanding reaction that requires low-potential electrons and ATP; however, pathways used to deliver the electrons from central metabolism to the reductants of nitrogenase, ferredoxin or flavodoxin, remain unknown for many diazotrophic microbes. The FixABCX protein complex has been proposed to reduce fla ...
DOI:
10.1021/acs.biochem.7b00389

84. Electrostatic Repulsion between Unique Arginine Residues Is Essential for the Efficient in Vitro Assembly of the Transmembrane Domain of a Trimeric Autotransporter

Author:
Aoki Eriko; Sato Daisuke; Fujiwara Kazuo; Ikeguchi Masamichi
Source:
Biochemistry 2017 v.56 no.15 pp. 2139-2148
ISSN:
1520-4995
Subject:
Haemophilus influenzae; adhesins; arginine; bacteria; detergents; electrostatic interactions; epithelial cells; lysine; methionine; mutants
Abstract:
... Haemophilus influenzae adhesin (Hia) belongs to the trimeric autotransporter family and mediates the adherence of these bacteria to the epithelial cells of host organisms. Hia contains a passenger and a transmembrane domain. The transmembrane domain forms a 12-stranded β-barrel in which four strands are provided by each subunit. The β-barrel has a pore that is traversed by three α-helices. This do ...
DOI:
10.1021/acs.biochem.6b01130

85. Elucidation of the Recognition Sequence of Sortase B from Bacillus anthracis by Using a Newly Developed Liquid Chromatography–Mass Spectrometry-Based Method

Author:
Puorger Chasper; Di Girolamo Salvatore; Lipps Georg
Source:
Biochemistry 2017 v.56 no.21 pp. 2641-2650
ISSN:
1520-4995
Subject:
Bacillus anthracis; Gram-positive bacteria; Staphylococcus aureus; amino acid sequences; cell walls; liquid chromatography; mass spectrometry; peptides; peptidoglycans; protein engineering; protein secretion; sortase B; streptavidin
Abstract:
... Sortases are enzymes that are responsible for the attachment of secreted proteins to the cell wall of Gram-positive bacteria. Hereby, the sortases recognize short, five-residue amino acid sequences present in the target proteins and fuse them to the peptidoglycan layer via a transpeptidation reaction, creating a new peptide bond between the C-terminus of the recognition sequence and the cell wall. ...
DOI:
10.1021/acs.biochem.7b00108

86. Encapsulation and Controlled Release of Protein Guests by the Bacillus subtilis Lumazine Synthase Capsid

Author:
Han Xue; Woycechowsky Kenneth J.
Source:
Biochemistry 2017 v.56 no.47 pp. 6211-6220
ISSN:
1520-4995
Subject:
Bacillus subtilis; amino acids; bacteria; capsid; dissociation; encapsulation; enzyme-linked immunosorbent assay; fluorescence; green fluorescent protein; pH; riboflavin
Abstract:
... In Bacillus subtilis, the 60-subunit dodecahedral capsid formed by lumazine synthase (BsLS) acts as a container for trimeric riboflavin synthase (BsRS). To test whether the C-terminal sequence of BsRS is responsible for its encapsulation by BsLS, the green fluorescent protein (GFP) was fused to either the last 11 or the last 32 amino acids of BsRS, yielding variant GFP11 or GFP32, respectively. Af ...
DOI:
10.1021/acs.biochem.7b00669

87. Endocannabinoid Interaction with Human FABP1: Impact of the T94A Variant

Author:
Martin Gregory G.; Huang Huan; McIntosh Avery L.; Kier Ann B.; Schroeder Friedhelm
Source:
Biochemistry 2017 v.56 no.38 pp. 5147-5159
ISSN:
1520-4995
Subject:
circular dichroism spectroscopy; fatty acid-binding proteins; fatty liver; fluorescence; humans; hydrophobicity; ligands; lipids
Abstract:
... Using recombinant human wild-type fatty acid binding protein 1 (WT FABP1 T94T) and a variant (FABP1 T94A) protein, fluorescence binding assays, and circular dichroism, it was shown for the first time that WT FABP1 and the T94A variant each have a single, relatively hydrophobic site for binding fluorescent NBD-labeled analogues of N-arachidonoylethanolamide and 2-arachidonoylglycerol with high affi ...
DOI:
10.1021/acs.biochem.7b00647

88. Engineering Aromatic–Aromatic Interactions To Nucleate Folding in Intrinsically Disordered Regions of Proteins

Author:
Balakrishnan Swati; Sarma Siddhartha P.
Source:
Biochemistry 2017 v.56 no.33 pp. 4346-4359
ISSN:
1520-4995
Subject:
bioinformatics; denaturation; engineering; hydrogen bonding; hydrophobic bonding; models; mutants; peptides; protein folding; proteins; urea
Abstract:
... Aromatic interactions are an important force in protein folding as they combine the stability of a hydrophobic interaction with the selectivity of a hydrogen bond. Much of our understanding of aromatic interactions comes from “bioinformatics” based analyses of protein structures and from the contribution of these interactions to stabilizing secondary structure motifs in model peptides. In this stu ...
DOI:
10.1021/acs.biochem.7b00437

89. Enhanced Binding Affinity via Destabilization of the Unbound State: A Millisecond Hydrogen–Deuterium Exchange Study of the Interaction between p53 and a Pleckstrin Homology Domain

Author:
Zhu Shaolong; Khatun Rahima; Lento Cristina; Sheng Yi; Wilson Derek J.
Source:
Biochemistry 2017 v.56 no.32 pp. 4127-4133
ISSN:
1520-4995
Subject:
Gibbs free energy; binding capacity; ionization; phosphorylation; pleckstrin; sequence homology; transcriptional activation
Abstract:
... The incorporation of intrinsically disordered domains enables proteins to engage a wide variety of targets, with phosphorylation often modulating target specificity and affinity. Although phosphorylation can clearly act as a chemical driver of complexation in structured proteins, e.g., by abrogating or permitting new charge–charge interactions, the basis for enhancement of the hydrophobically driv ...
DOI:
10.1021/acs.biochem.7b00193

90. Enormous Hydrogen Bond Strength Enhancement through π-Conjugation Gain: Implications for Enzyme Catalysis

Author:
Wu Chia-Hua; Ito Keigo; Buytendyk Allyson M.; Bowen K. H.; Wu Judy I.
Source:
Biochemistry 2017 v.56 no.33 pp. 4318-4322
ISSN:
1520-4995
Subject:
catalytic activity; enzymes; hydrogen bonding; models; oxyanions
Abstract:
... Surprisingly large resonance-assistance effects may explain how some enzymes form extremely short, strong hydrogen bonds to stabilize reactive oxyanion intermediates and facilitate catalysis. Computational models for several enzymic residue–substrate interactions reveal that when a π-conjugated, hydrogen bond donor (XH) forms a hydrogen bond to a charged substrate (Y–), XH can become significantly ...
DOI:
10.1021/acs.biochem.7b00395

91. Entry of a Six-Residue Antimicrobial Peptide Derived from Lactoferricin B into Single Vesicles and Escherichia coli Cells without Damaging their Membranes

Author:
Moniruzzaman Md.; Islam Md. Zahidul; Sharmin Sabrina; Dohra Hideo; Yamazaki Masahito
Source:
Biochemistry 2017 v.56 no.33 pp. 4419-4431
ISSN:
1520-4995
Subject:
DNA; Escherichia coli; antimicrobial peptides; antimicrobial properties; bacteria; confocal microscopy; cytoplasm; fluorescence; fluorescent dyes; lipids; plasma membrane
Abstract:
... Lactoferricin B (LfcinB) and shorter versions of this peptide have antimicrobial activity. However, the elementary processes of interactions of these peptides with lipid membranes and bacteria are still not well understood. To elucidate the mechanism of their antimicrobial activity, we investigated the interactions of LfcinB (4–9) (its sequence of RRWQWR) with Escherichia coli cells and giant unil ...
DOI:
10.1021/acs.biochem.6b01274

92. Enzymatic Cross-Linking of Side Chains Generates a Modified Peptide with Four Hairpin-like Bicyclic Repeats

Author:
Lee Hyunbin; Park Youngseon; Kim Seokhee
Source:
Biochemistry 2017 v.56 no.37 pp. 4927-4930
ISSN:
1520-4995
Subject:
bioactive properties; biosynthesis; consensus sequence; crosslinking; cyclic peptides; drugs; engineering; esterification; proteinases; signal peptide; tandem mass spectrometry
Abstract:
... Macrocyclization of peptides is often employed to generate novel structures and biological activities in the biosynthesis of natural products and drug discovery. The enzymatic cross-linking of two side chains in a peptide via an ester or amide has a high potential for making topologically diverse cyclic peptides but is found with only a single consensus sequence in the microviridin class of natura ...
DOI:
10.1021/acs.biochem.7b00808

93. Enzyme-Mediated Conversion of Flavin Adenine Dinucleotide (FAD) to 8-Formyl FAD in Formate Oxidase Results in a Modified Cofactor with Enhanced Catalytic Properties

Author:
John M. Robbins; Michael G. Souffrant; Donald Hamelberg; Giovanni Gadda; Andreas S. Bommarius
Source:
Biochemistry 2017 v.56 no.29 pp. 3800-3807
ISSN:
1520-4995
Subject:
arginine; catalytic activity; circular dichroism spectroscopy; enzyme activity; flavin-adenine dinucleotide; flavoproteins; fluorescence emission spectroscopy; formates; fungi; lactate 2-monooxygenase; liquid chromatography; mass spectrometry; site-directed mutagenesis
Abstract:
... Flavins, including flavin adenine dinucleotide (FAD), are fundamental catalytic cofactors that are responsible for the redox functionality of a diverse set of proteins. Alternatively, modified flavin analogues are rarely found in nature as their incorporation typically results in inactivation of flavoproteins, thus leading to the disruption of important cellular pathways. Here, we report that the ...
DOI:
10.1021/acs.biochem.7b00335

94. Eukaryotic Ribosomal Expansion Segments as Antimicrobial Targets

Author:
Gómez Ramos Lizzette M.; Degtyareva Natalya N.; Kovacs Nicholas A.; Holguin Stefany Y.; Jiang Liuwei; Petrov Anton S.; Biesiada Marcin; Hu Michael Y.; Purzycka Katarzyna J.; Arya Dev P.; Williams Loren Dean
Source:
Biochemistry 2017 v.56 no.40 pp. 5288-5299
ISSN:
1520-4995
Subject:
Candida albicans; cytotoxicity; drug therapy; drugs; fluorescence; fluorescent dyes; fungi; humans; minimum inhibitory concentration; mortality; pathogens; prokaryotic cells; ribosomal RNA; ribosomes
Abstract:
... Diversity in eukaryotic rRNA structure and function offers possibilities of therapeutic targets. Unlike ribosomes of prokaryotes, eukaryotic ribosomes contain species-specific rRNA expansion segments (ESs) with idiosyncratic structures and functions that are essential and specific to some organisms. Here we investigate expansion segment 7 (ES7), one of the largest and most variable expansions of t ...
DOI:
10.1021/acs.biochem.7b00703

95. Evidence from FTIR Difference Spectroscopy That a Substrate H2O Molecule for O2 Formation in Photosystem II Is Provided by the Ca Ion of the Catalytic Mn4CaO5 Cluster

Author:
Kim Christopher J.; Debus Richard J.
Source:
Biochemistry 2017 v.56 no.20 pp. 2558-2570
ISSN:
1520-4995
Subject:
Fourier transform infrared spectroscopy; calcium; catalysts; hydrogen bonding; models; oxygen; photosystem II; strontium
Abstract:
... The O₂-producing Mn₄CaO₅ catalyst in photosystem II oxidizes two water molecules (substrate) to produce one O₂ molecule. Considerable evidence supports the identification of one of the two substrate waters as the Mn₄CaO₅ cluster’s oxo bridge known as O₅. The identity of the second substrate water molecule is less clear. In one set of models, the second substrate is the Mn-bound water molecule know ...
DOI:
10.1021/acs.biochem.6b01278

96. Exosite 2-Directed Ligands Attenuate Protein C Activation by the Thrombin–Thrombomodulin Complex

Author:
Chen Kai; Stafford Alan R.; Wu Chengliang; Yeh Calvin H.; Kim Paul Y.; Fredenburgh James C.; Weitz Jeffrey I.
Source:
Biochemistry 2017 v.56 no.24 pp. 3119-3128
ISSN:
1520-4995
Subject:
active sites; anticoagulants; endothelial cells; fibrin; fibrinogen; glycoproteins; ligands; oligonucleotides; thrombin
Abstract:
... Thrombin activity, inhibition, and localization are regulated by two exosites that flank the active site. Substrates, cofactors, and inhibitors bind to exosite 1 to promote active site access, whereas exosite 2 interactions hold thrombin on cells, platelets, and proteins. The exosites also serve allosteric roles, whereby ligand binding alters thrombin activity. Previously, we showed that ligands t ...
DOI:
10.1021/acs.biochem.7b00250

97. Exosomes Secreted by HeLa Cells Shuttle on Their Surface the Plasma Membrane-Associated Sialidase NEU3

Author:
Paolini Lucia; Orizio Flavia; Busatto Sara; Radeghieri Annalisa; Bresciani Roberto; Bergese Paolo; Monti Eugenio
Source:
Biochemistry 2017 v.56 no.48 pp. 6401-6408
ISSN:
1520-4995
Subject:
Western blotting; biological properties and phenomena; blood; cell communication; cell differentiation; culture media; diagnostic techniques; enzyme activity; exosomes; glycolipids; glycoproteins; human cell lines; mice; nanomedicine; neoplasms; oligosaccharides; polysaccharides; sialic acid; sialidase; urine
Abstract:
... Sialidases are glycohydrolases that remove terminal sialic acid residues from oligosaccharides, glycolipids, and glycoproteins. The plasma membrane-associated sialidase NEU3 is involved in the fine-tuning of sialic acid-containing glycans directly on the cell surface and plays relevant roles in important biological phenomena such as cell differentiation, molecular recognition, and cancer transform ...
DOI:
10.1021/acs.biochem.7b00665

98. Expanding the Genetic Code of a Photoautotrophic Organism

Author:
Chemla Yonatan; Friedman Mor; Heltberg Mathias; Bakhrat Anna; Nagar Elad; Schwarz Rakefet; Jensen Mogens Høgh; Alfonta Lital
Source:
Biochemistry 2017 v.56 no.16 pp. 2161-2165
ISSN:
1520-4995
Subject:
stop codon; green fluorescent protein; translation (genetics); genetic code; Synechococcus elongatus; models; amino acids; photosynthesis
Abstract:
... The photoautotrophic freshwater cyanobacterium Synechococcus elongatus is widely used as a chassis for biotechnological applications as well as a photosynthetic bacterial model. In this study, a method for expanding the genetic code of this cyanobacterium has been established, thereby allowing the incorporation of unnatural amino acids into proteins. This was achieved through UAG stop codon suppre ...
DOI:
10.1021/acs.biochem.7b00131

99. Exploration of the Innate Immune System of Styela clava: Zn2+ Binding Enhances the Antimicrobial Activity of the Tunicate Peptide Clavanin A

Author:
Juliano Samuel A.; Pierce Scott; deMayo James A.; Balunas Marcy J.; Angeles-Boza Alfredo M.
Source:
Biochemistry 2017 v.56 no.10 pp. 1403-1414
ISSN:
1520-4995
Subject:
Escherichia coli; Styela clava; antimicrobial peptides; antimicrobial properties; bacteria; beta-galactosidase; cell death; cell membranes; confocal microscopy; humoral immunity; immune response; innate immunity; ions; models; mutants; potassium; synergism; zinc
Abstract:
... Tunicates have been used as primitive models for understanding cell-mediated and humoral immunity. Clavanin A (ClavA) is one member of a family of antimicrobial peptides produced by the solitary tunicate Styela clava. In this work, we demonstrate that ClavA utilizes Zn²⁺ ions to potentiate its antimicrobial activity not only by reducing the concentration at which the peptide inhibits the growth of ...
DOI:
10.1021/acs.biochem.6b01046

100. Expression and Purification of ZASP Subdomains and Clinically Important Isoforms: High-Affinity Binding to G-Actin

Author:
Watts Norman R.; Zhuang Xiaolei; Kaufman Joshua D.; Palmer Ira W.; Dearborn Altaira D.; Coscia Stephen; Blech-Hermoni Yotam; Alfano Caterina; Pastore Annalisa; Mankodi Ami; Wingfield Paul T.
Source:
Biochemistry 2017 v.56 no.14 pp. 2061-2070
ISSN:
1520-4995
Subject:
actin; alternative splicing; electron microscopy; exons; ionic strength; ions; magnesium; muscular diseases; mutants; mutation; nuclear magnetic resonance spectroscopy; potassium chloride; sarcomeres; skeletal muscle; surface plasmon resonance
Abstract:
... Z-disc-associated, alternatively spliced, PDZ motif-containing protein (ZASP) is a principal component of the sarcomere. The three prevalent isoforms of ZASP in skeletal muscle are generated by alternative splicing of exons 9 and 10. The long isoforms, either having (ZASP-L) or lacking exon 10 (ZASP-LΔex10), include an N-terminal PDZ domain, an actin-binding region (ABR) with a conserved motif (ZM ...
DOI:
10.1021/acs.biochem.7b00067