Computational Insights into the Allosteric Modulation of a Phthalate-Degrading Hydrolase by Distal Mutations.

ABSTRACT: Phthalate esters (PAEs) are a ubiquitous kind of environmental endocrine that disrupt chemicals, causing environmental and health issues. EstJ6 is an effective phthalate-degrading hydrolase, and its mutant with a combination of three non-conservative distal mutations has an improved activity against PAEs with unknown molecular mechanisms. Herein, we attempt to fill the significant gap between distal mutations and the activity of this enzyme using computational approaches. We found that mutations resulted in a redistribution of the enzyme's preexisting conformational states and dynamic changes of key functional regions, especially the lid over the active site. The outward motion of the lid upon the mutations made it easier for substrates or products to enter or exit. Additionally, a stronge

SUBMITTER: Xu R 

PROVIDER: S-EPMC10046322 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature