Molecular basis of rutin inhibition of protein disulfide isomerase (PDI) by combined in silico and experimental methods.

ABSTRACT: Protein disulfide isomerase (PDI) is a founding member of the thiol isomerase family, and is recently found to play critical roles in thrombus formation. The development of effective PDI inhibitors is of great significance, and attracts strong interest. We previously showed that rutin bound directly to PDI and inhibited PDI activities, leading to the suppression of platelet aggregation and fibrin generation in a mouse model. A close analog of rutin, isoquercetin, is currently in advanced phase clinical trials. However, the molecular interaction between rutin and PDI is unknown and is difficult to study by X-ray crystallography due to the weak interaction. Here, we generated a molecular model of PDI:rutin complex by molecular docking and thorough molecular dynamics (MD) simulations. We then

SUBMITTER: Wang X 

PROVIDER: S-EPMC9080521 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature