Quantitative Correlation of Conformational Binding Enthalpy with Substrate Specificity of Serine Proteases.

ABSTRACT: Members of the same protease family show different substrate specificity, even if they share identical folds, depending on the physiological processes they are part of. Here, we investigate the key factors for subpocket and global specificity of factor Xa, elastase, and granzyme B which despite all being serine proteases and sharing the chymotrypsin-fold show distinct substrate specificity profiles. We determined subpocket interaction potentials with GRID for static X-ray structures and an in silico generated ensemble of conformations. Subpocket interaction potentials determined for static X-ray structures turned out to be insufficient to explain serine protease specificity for all subpockets. Therefore, we generated conformational ensembles using molecular dynamics simulations. We identif

SUBMITTER: Waldner BJ 

PROVIDER: S-EPMC4724848 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature