Mutational effects of Cys113 on structural dynamics of Pin1.

ABSTRACT: Pin1 is a peptidyl-prolyl isomerase (PPIase) which catalyzes cis/trans isomerization of pS/pT-P bond. Its activity is related to various cellular functions including suppression of Alzheimer's disease. A cysteine residue C113 is known to be important for its PPIase activity; a mutation C113A reduced the activity by 130-fold. According to various nuclear magnetic resonance experiments for mutants of C113 and molecular dynamics (MD) simulation of wild-type Pin1, the protonation sate of Sγ of C113 regulates the hydrogen-bonding network of the dual-histidine motif (H59, H157) whose dynamics may affect substrate binding ability. However, it was still unclear why such local dynamic changes altered the PPIase activity of Pin1. In this study, we performed 500 ns of MD simulations of full-le

SUBMITTER: Ikura T 

PROVIDER: S-EPMC6976032 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature