Role of Enzyme and Active Site Conformational Dynamics in the Catalysis by α-Amylase Explored with QM/MM Molecular Dynamics.

ABSTRACT: We assessed enzyme:substrate conformational dynamics and the rate-limiting glycosylation step of a human pancreatic α-amylase:maltopentose complex. Microsecond molecular dynamics simulations suggested that the distance of the catalytic Asp197 nucleophile to the anomeric carbon of the buried glucoside is responsible for most of the enzyme active site fluctuations and that both Asp197 and Asp300 interact the most with the buried glucoside unit. The buried glucoside binds either in a ⁴C₁ chair or ²S_O skew conformations, both of which can change to TS-like conformations characteristic of retaining glucosidases. Starting from four distinct enzyme:substrate complexes, umbrella sampling quantum mechanics/molecular mechanics simulati

SUBMITTER: Neves RPP 

PROVIDER: S-EPMC9778734 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature