title: Tautomeric Effect of Histidine on the Monomeric Structure of Amyloid β-Peptide(1-42).
abstract: Tautomeric state of histidine is one of the factors that influence the structural and aggregation properties of amyloid β (Aβ)-peptide in neutral state. It is worth it to uncover the monomeric properties of Aβ(1-42) peptide in comparison with Aβ(1-40) peptide. Our replica-exchange molecular dynamics simulations results show that the sheet content of each tautomeric isomer in Aβ(1-42) monomer is slightly higher than that in Aβ(1-40) monomer except His6(δ)-His13(δ)-His14(δ) (δδδ) isomer, implying higher aggregation tendency in Aβ(1-42), which is in agreement with previous experimental and theoretical studies. Further analysis indicates that (εεε), (εδε), (εδδ), and (δδε) isomers prefer sheet conformation although they are in nondominating states. Particularly, it is confirmed that antiparallel β-sheets of (εδδ) were formed at K16-E22 (22.0-43.9%), N27-A30 except G29 (21.9-40.2%), and M35-I41 except G37 (24.1-43.4%). Furthermore, (εδδ) may be the easiest one to overcome structural transformation due to nonobstructing interactions between K16 and/or L17 and histidine residues. The current study will help to understand the tautomeric effect of Aβ(1-42) peptide to overcome Alzheimer's disease.
authors.affiliation: Department of Chemistry, Sungkyunkwan University , Suwon 440-746, Korea.
authors.forename: Hu
authors.identifier: 0000-0002-5466-5783
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Chemistry, Sungkyunkwan University , Suwon 440-746, Korea.
authors.forename: Jin Yong
authors.identifier: 0000-0003-0360-5059
authors.initials: JY
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D006639:Histidine / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D017510:Protein Folding; D017433:Protein Structure, Secondary
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D006639:Histidine
keywords: Tautomeric effect; aggregation; amyloid(1−42) peptide; histidine tautomer; protein misfolding; sheet structure