%0 Journal Article
%T Tautomerization Effect of Histidines on Oligomer Aggregation of ¦Â-Amyloid(1¨C40/42) during the Early Stage: Tautomerism Hypothesis for Misfolding Protein Aggregation
%J -
%D 2019
%R https://doi.org/10.1021/acschemneuro.9b00094
%X As the intrinsic origin of the hypothesis for ¦Â-amyloid (A¦Â) from Alzheimer¡¯s disease, histidine behaviors were found to play a crucial role in A¦Â aggregation. To investigate the histidine behaviors during the early stage of aggregation, A¦Â40/42 pentamers with different histidine isomer states were simulated at the atomic level. Results show that five A¦Â40 (¦Ä¦Ä¦Ä) and A¦Â42 (¦Å¦Ä¦Ä) monomers can rapidly decrease the aggregation threshold, promote stable pentamer formation, and increase pentamer contents by 51.8% and 56.7%, respectively, as compared with the values of their wild-type (¦Å¦Å¦Å) counterparts. Additionally, pentamers of A¦Â40 (¦Ä¦Ä¦Ä) and A¦Â42 (¦Å¦Ä¦Ä) have different aggregation pathways and disassembly species, Tr+D and Te+M, during the growth of the pentamer. This work discloses the significance of histidine tautomerization in A¦Â aggregation, implying a potential way to control A¦Â aggregation and develop the assembly inhibitors
%U https://pubs.acs.org/doi/10.1021/acschemneuro.9b00094