Crystal structure of thrombin bound to the uncleaved extracellular fragment of PAR1.

ABSTRACT: Abundant structural information exists on how thrombin recognizes ligands at the active site or at exosites separate from the active site region, but remarkably little is known about how thrombin recognizes substrates that bridge both the active site and exosite I. The case of the protease-activated receptor PAR1 is particularly relevant in view of the plethora of biological effects associated with its activation by thrombin. Here, we present the 1.8 A resolution structure of thrombin S195A in complex with a 30-residue long uncleaved extracellular fragment of PAR1 that documents for the first time a productive binding mode bridging the active site and exosite I. The structure reveals two unexpected features of the thrombin-PAR1 interaction. The acidic P3 residue of PAR1, Asp(39), does not

SUBMITTER: Gandhi PS 

PROVIDER: S-EPMC2865304 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature