Mechanistic basis of activation and inhibition of protein disulfide isomerase by allosteric antithrombotic compounds.

ABSTRACT:

Background

Protein disulfide isomerase (PDI) is a promising target for combating thrombosis. Extensive research over the past decade has identified numerous PDI-targeting compounds. However, limited information exists regarding how these compounds control PDI activity, which complicates further development.

Objectives

To define the mechanism of action of 2 allosteric antithrombotic compounds of therapeutic interest, quercetin-3-O-rutinoside and bepristat-2a.

Methods

A multipronged approach that integrates single-molecule spectroscopy, steady-state kinetics, single-turnover kinetics, and site-specific mutagenesis.

Results

PDI is a thiol isomerase consisting of 2 catalytic a domains and 2 inactive b domains arranged in the order a-b-b'-a'. The active sites CGHC a

SUBMITTER: Ponzar N 

PROVIDER: S-EPMC11786983 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature