CRYSTALLOGRAPHIC EVIDENCE THAT THE F2 KRINGLE CATALYTIC DOMAIN LINKEROF PROTHROMBIN DOES NOT COVER THE FIBRINOGEN RECOGNITION EXOSITE

The 2.6-Angstrom x-ray crystal structure of bovine alpha-thrombin in c omplex with rhodniin, a protein inhibitor isolated from the bug Rhodni us prolixus, has been solved and refined. The structure has enabled us to trace the N-terminal part of the 49-residue A-chain of bovine alph a-thrombin for the first time, which is fixed in a U-shaped loop on th e molecular surface opposite the active site canyon. Model building sh ows that the 25 amino acid residues that link the A-chain and F2 kring le cannot run through the fibrinogen recognition exosite. This demonst rates that this fibrinogen recognition exosite is available in prothro mbin and meizothrombin.