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Biochemistry
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2018
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2018 v.57 no.46
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- Author:
- Offutt, Tavina L.; Ieong, Pek U.; Demir, Özlem; Amaro, Rommie E.
- Source:
- Biochemistry 2018 v.57 no.46 pp. 6528-6537
- ISSN:
- 1520-4995
- Subject:
- DNA; DNA damage; DNA-binding domains; apoptosis; asymmetry; cell cycle checkpoints; crystal structure; drug resistance; genome; genomics; humans; hypoxia; models; molecular dynamics; mutants; neoplasms; site-directed mutagenesis; transcription factors; transcriptional activation
- Abstract:
- ... The “guardian of the genome”, p53, functions as a tumor suppressor that responds to cell stressors such as DNA damage, hypoxia, and tumor formation by inducing cell-cycle arrest, senescence, or apoptosis. Mutation of p53 disrupts its tumor suppressor function, leading to various types of human cancers. One particular mutant, R175H, is a structural mutant that inactivates the DNA damage response pa ...
- DOI:
- 10.1021/acs.biochem.8b01005
- http://dx.doi.org/10.1021/acs.biochem.8b01005
- Author:
- Cai, Fangze; Hwang, Peter M.; Sykes, Brian D.
- Source:
- Biochemistry 2018 v.57 no.46 pp. 6461-6469
- ISSN:
- 1520-4995
- Subject:
- calcium; chemical bonding; electrostatic interactions; heart diseases; hydrophobicity; mice; naphthalene; nuclear magnetic resonance spectroscopy; peptides; regulatory proteins; sarcomeres; solvents; transgenic animals; troponin C; troponin I
- Abstract:
- ... Compounds that directly modulate the affinity of the thin filament calcium regulatory proteins in cardiac muscle have potential for treating heart disease. A recent “proof of concept” study showed that the desensitizer W7 can correct hyper-calcium-sensitive sarcomeres from RCM R193H inhibitory subunit troponin I (cTnI) transgenic mice. We have determined the high-resolution nuclear magnetic resona ...
- DOI:
- 10.1021/acs.biochem.8b00882
- http://dx.doi.org/10.1021/acs.biochem.8b00882
- Author:
- Buchanan, Lauren E.; Maj, Michał; Dunkelberger, Emily B.; Cheng, Pin-Nan; Nowick, James S.; Zanni, Martin T.
- Source:
- Biochemistry 2018 v.57 no.46 pp. 6470-6478
- ISSN:
- 1520-4995
- Subject:
- Gibbs free energy; amyloid; cytotoxicity; drugs; humans; infrared spectroscopy; noninsulin-dependent diabetes mellitus; polypeptides; seeds
- Abstract:
- ... It is now recognized that many amyloid-forming proteins can associate into multiple fibril structures. Here, we use two-dimensional infrared spectroscopy to study two fibril polymorphs formed by human islet amyloid polypeptide (hIAPP or amylin), which is associated with type 2 diabetes. The polymorphs exhibit different degrees of structural organization near the loop region of hIAPP fibrils. The r ...
- DOI:
- 10.1021/acs.biochem.8b00997
- PubMed:
- 30375231
- PubMed Central:
- PMC6368979
- http://dx.doi.org/10.1021/acs.biochem.8b00997
- Author:
- Chilakamarthi, Ushasri; Koteshwar, Devulapally; Jinka, Sudhakar; Vamsi Krishna, Narra; Sridharan, Kathyayani; Nagesh, Narayana; Giribabu, Lingamallu
- Source:
- Biochemistry 2018 v.57 no.46 pp. 6514-6527
- ISSN:
- 1520-4995
- Subject:
- DNA; adverse effects; antineoplastic agents; apoptosis; binding capacity; cell cycle checkpoints; cell lines; cell proliferation; cytotoxicity; drug therapy; fluorescence; irradiation; melting; neoplasm cells; neoplasms; porphyrins; spectroscopy; tissues
- Abstract:
- ... Porphyrins are well-known anticancer agents because of their high binding affinity for G-quadruplex DNA and excellent photophysical properties. Several studies carried out using TMPyP4 established it as an efficient chemotherapeutic and a photodynamic therapeutic (PDT) agent, but its use as a lead molecule has been restricted because of its high level of binding to double-stranded DNA (dsDNA), whi ...
- DOI:
- 10.1021/acs.biochem.8b00843
- http://dx.doi.org/10.1021/acs.biochem.8b00843
- Author:
- Noell, Crystal R.; Loftus, Kyle M.; Cui, Heying; Grewer, Christof; Kizer, Megan; Debler, Erik W.; Solmaz, Sozanne R.
- Source:
- Biochemistry 2018 v.57 no.46 pp. 6538-6550
- ISSN:
- 1520-4995
- Subject:
- brain; dynein ATPase; humans; interphase; models; nuclear pore; prediction; proteins; synapse
- Abstract:
- ... Dynein adaptor proteins such as Bicaudal D2 (BicD2) are integral components of the dynein transport machinery, as they recognize cargoes for cell cycle-specific transport and link them to the motor complex. Human BicD2 switches from selecting secretory and Golgi-derived vesicles for transport in G1 and S phase (by recognizing Rab6ᴳᵀᴾ), to selecting the nucleus for transport in G2 phase (by recogni ...
- DOI:
- 10.1021/acs.biochem.8b00987
- PubMed:
- 30345745
- PubMed Central:
- PMC6520106
- http://dx.doi.org/10.1021/acs.biochem.8b00987
- Author:
- Dunham, Noah P.; Mitchell, Andrew J.; Del Río Pantoja, José M.; Krebs, Carsten; Bollinger, J. Martin; Boal, Amie K.
- Source:
- Biochemistry 2018 v.57 no.46 pp. 6479-6488
- ISSN:
- 1520-4995
- Subject:
- ammonia; arginine; carbon; catalytic activity; chemical bonding; cleavage (chemistry); deamination; deuterium; enantiomers; formaldehyde; hydroxylation; iron; moieties; oxygen; oxygenases; solvents; stable isotopes
- Abstract:
- ... When challenged with substrate analogues, iron(II)- and 2-(oxo)glutarate-dependent (Fe/2OG) oxygenases can promote transformations different from those they enact upon their native substrates. We show here that the Fe/2OG enzyme, VioC, which is natively an l-arginine 3-hydroxylase, catalyzes an efficient oxidative deamination of its substrate enantiomer, d-Arg. The reactant complex with d-Arg reta ...
- DOI:
- 10.1021/acs.biochem.8b00901
- PubMed:
- 30403469
- PubMed Central:
- PMC6424487
- http://dx.doi.org/10.1021/acs.biochem.8b00901
7. Endocannabinoid Virodhamine Is an Endogenous Inhibitor of Human Cardiovascular CYP2J2 Epoxygenase
- Author:
- Carnevale, Lauren N.; Arango, Andres S.; Arnold, William R.; Tajkhorshid, Emad; Das, Aditi
- Source:
- Biochemistry 2018 v.57 no.46 pp. 6489-6499
- ISSN:
- 1520-4995
- Subject:
- arachidonic acid; bioactive compounds; blood pressure; cannabinoids; catalytic activity; constitutional isomers; cytochrome P-450; enzymes; epoxides; ethanolamine; heart; humans; metabolism; molecular dynamics; swine
- Abstract:
- ... The human body contains endogenous cannabinoids (endocannabinoids) that elicit effects similar to those of Δ⁹-tetrahydrocanabinol, the principal bioactive component of cannabis. The endocannabinoid virodhamine (O-AEA) is the constitutional isomer of the well-characterized cardioprotective and anti-inflammatory endocannabinoid anandamide (AEA). The chemical structures of O-AEA and AEA contain arach ...
- DOI:
- 10.1021/acs.biochem.8b00691
- PubMed:
- 30285425
- PubMed Central:
- PMC6262108
- http://dx.doi.org/10.1021/acs.biochem.8b00691
- Author:
- Surnar, Bapurao; Kolishetti, Nagesh; Basu, Uttara; Ahmad, Anis; Goka, Erik; Marples, Brian; Kolb, David; Lippman, Marc E.; Dhar, Shanta
- Source:
- Biochemistry 2018 v.57 no.46 pp. 6500-6513
- ISSN:
- 1520-4995
- Subject:
- DNA; DNA damage; adverse effects; antineoplastic activity; aspirin; cisplatin; drug therapy; in vitro studies; models; nausea; nephrotoxicity; neurotoxicity; patients; urinary bladder neoplasms
- Abstract:
- ... Cisplatin is a major chemotherapeutic that continues to have a significant impact in the treatment of more than 50% of all cancers. Since its Food and Drug Administration approval in 1978 for the treatment of advanced ovarian and bladder cancer, this chemotherapeutic has made significant strides and its application has been extended to a large variety of other cancers. However, the vast majority o ...
- DOI:
- 10.1021/acs.biochem.8b00712
- http://dx.doi.org/10.1021/acs.biochem.8b00712