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Tautomeric Effect of Histidine on the Monomeric Structure of Amyloid β-Peptide(1–40) B

Author:
Shi, Hu, Kang, Baotao, Lee, Jin Yong
Source:
The Journal of physical chemistry 2016 v.120 no.44 pp. 11405-11411
ISSN:
1520-5207
Subject:
Alzheimer disease, amyloid, histidine, isomers, molecular dynamics, pathogenesis
Abstract:
Histidine state (deprotonated, neutral, and protonated) is considered an important factor influencing the structural properties and aggregation mechanisms in amyloid β-peptides (Aβ), which are associated with the pathogenesis of Alzheimer’s disease. Understanding the structural properties and aggregation mechanisms is a great challenge because two forms (the Nᵋ–H or Nᵟ–H tautomer) can exist in the free neutral state of histidine. Here, replica-exchange molecular dynamics simulation was performed to elucidate the changes in structure and the mechanism of aggregation influenced by tautomeric behaviors of histidine in Aβ(1–40). Our results show that sheet-dominating conformations can be found in the His6(δ)–His13(δ)–His14(δ) (δδδ) isomer with significant antiparallel sheet structures between R5–D7 and L34–G38, as well as between L17–F20 and L34–G38, implying that a new aggregation mechanism may exist to promote the generation of oligomers and/or aggregates. This work is helpful in understanding the fundamental tautomeric behaviors of neutral histidine in the process of aggregation.
Agid:
5622811