Specificity and affinity of the N-terminal residues in staphylocoagulase in binding to prothrombin.

ABSTRACT: In Staphylococcus aureus-caused endocarditis, the pathogen secretes staphylocoagulase (SC), thereby activating human prothrombin (ProT) and evading immune clearance. A previous structural comparison of the SC(1-325) fragment bound to thrombin and its inactive precursor prethrombin 2 has indicated that SC activates ProT by inserting its N-terminal dipeptide Ile¹-Val² into the ProT Ile¹⁶ pocket, forming a salt bridge with ProT's Asp¹⁹⁴, thereby stabilizing the active conformation. We hypothesized that these N-terminal SC residues modulate ProT binding and activation. Here, we generated labeled SC(1-246) as a probe for competitively defining the affinities of N-terminal SC(1-246) variants preselected by modeling. Using ProT(R155Q,R271Q,R284Q)

SUBMITTER: Maddur AA 

PROVIDER: S-EPMC7186164 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature