Insight into the broadened substrate scope of nitrile hydratase by static and dynamic structure analysis.

ABSTRACT: The narrow substrate scope limits the wide industrial application of enzymes. Here, we successfully broadened the substrate scope of a nitrile hydratase (NHase) through mutation of two tunnel entrance residues based on rational tunnel calculation. Two variants, with increased specific activity, especially toward bulky substrates, were obtained. Crystal structure analysis revealed that the mutations led to the expansion of the tunnel entrance, which might be conducive to substrate entry. More importantly, molecular dynamics simulations illustrated that the mutations introduced anti-correlated movements to the regions around the substrate tunnel and the active site, which would promote substrate access during the dynamic process of catalysis. Additionally, mutations on the corresponding tunn

SUBMITTER: Ma D 

PROVIDER: S-EPMC9297474 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature