The region of the thrombin receptor resembling hirudin binds to thrombin and alters enzyme specificity.

摘要: A thrombin receptor has recently been cloned and the sequence deduced. The reveals a cleavage site that accounts for activation. also an acidic region with some similarities to carboxyl-terminal of leech inhibitor, hirudin. Synthetic peptides corresponding (residues 38-45), hirudin-like domain 52-69), covalently associated domains 38-64) were evaluated their ability bind thrombin. Peptides 38-45 38-64 competitive inhibitors thrombin's chromogenic substrate activity (Ki = 0.96 mM 0.6 microM, respectively. Residues 52-69 altered specificity, resulting in accelerated substrates inhibited others. same peptide binds alters fluorescence emission intensity 5-dimethylaminonaphthalene-1-sulfonyl (dansyl)-thrombin which dansyl is attached directly active serine (Kd 32 +/- 7 microM). displace hirudin, indicating they share common binding anion exosite These data suggest high affinity due presence this specificity This change may account serve as excellent despite Asp residue P3 site, normally inhibitory activity.