title: Tautomeric Effect of Histidine on the Monomeric Structure of Amyloid β-Peptide(1-40).
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 Nε-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.
authors.affiliation: Department of Chemistry, Sungkyunkwan University , Suwon 440-746, Korea.
authors.forename: Hu
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Chemistry and Chemical Engineering, University of Jinan , Jinan 250022, P. R. China.
authors.forename: Baotao
authors.initials: B
authors.lastname: Kang
authors.affiliation: Department of Chemistry, Sungkyunkwan University , Suwon 440-746, Korea.
authors.forename: Jin Yong
authors.initials: JY
authors.lastname: Lee
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D010446:Peptide Fragments / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D006639:Histidine