Structural bases of thrombin specificity. Role of secondary interactions
Kibirev, V.K.; Romanova, V.P.; Serebrianyĭ, S.B.
Biokhimiia 48(6): 937-943
1983
ISSN/ISBN: 0320-9725 PMID: 6882831 Document Number: 213520
The action of thrombin on the esters, Tos-P2-Arg-OCH3 and Tos-P3-P2-Arg-OCH3, where P2 and P3 are the residues of L-, D- or N-methylamino acids, has been studied. The values of kcat and Km(app) under steady-state conditions at pH 8.5 have been determined. The results obtained and literature data suggest that one of the causes of the low catalytic potency of thrombin is a decrease in the hydrophobicity of the environment of Asp-102 located at the active site of the enzyme. Therefore thrombin can cleave only the peptides which hydrophobically shield Asp-102. The key role in this process may be played by the side chains of the amino acids at P2 and P9, thus suggesting the presence of a beta-turn in the P7-P4 region of the polypeptide substrates of thrombin.