Exposure of R169 controls protein C activation and autoactivation.

ABSTRACT: Protein C is activated by thrombin with a value of k(cat)/K(m) = 0.11mM(-1)s(-1) that increases 1700-fold in the presence of the cofactor thrombomodulin. The molecular origin of this effect triggering an important feedback loop in the coagulation cascade remains elusive. Acidic residues in the activation domain of protein C are thought to electrostatically clash with the active site of thrombin. However, functional and structural data reported here support an alternative scenario. The thrombin precursor prethrombin-2 has R15 at the site of activation in ionic interaction with E14e, D14l, and E18, instead of being exposed to solvent for proteolytic attack. Residues E160, D167, and D172 around the site of activation at R169 of protein C occupy the same positions as E14e, D14l, and E18 in pre

SUBMITTER: Pozzi N 

PROVIDER: S-EPMC3401217 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature