Back to Search
Start Over
Tautomeric Effect of Histidine on the Monomeric Structure of Amyloid β-Peptide(1-40).
- Source :
-
The journal of physical chemistry. B [J Phys Chem B] 2016 Nov 10; Vol. 120 (44), pp. 11405-11411. Date of Electronic Publication: 2016 Oct 27. - Publication Year :
- 2016
-
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 N <superscript>ε</superscript> -H or N <superscript>δ</superscript> -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.
Details
- Language :
- English
- ISSN :
- 1520-5207
- Volume :
- 120
- Issue :
- 44
- Database :
- MEDLINE
- Journal :
- The journal of physical chemistry. B
- Publication Type :
- Academic Journal
- Accession number :
- 27750416
- Full Text :
- https://doi.org/10.1021/acs.jpcb.6b08685