PMID: 8961351Nov 1, 1996Paper

Homology modelling of rat kallikrein rK9, a member of the tissue kallikrein family: implications for substrate specificity and inhibitor binding

Protein Engineering
T Moreau, F Gauthier

Abstract

The rat kallikrein rK9 is one of the six members of the rat tissue kallikrein family isolated to date. It is 84% identical to rK2 (tonin), and both proteinases are thought to have vasoconstrictive properties. Recently we have shown that rK9 and rK2 have distinct substrate specificities and sensitivities to inhibitors, despite their similar sequences. Unlike all other mammalian kallikrein-related proteinases, rK9 is resistant to inhibition by aprotinin. We have developed a 3-D model of rK9, based on the known X-ray structures of rK2, porcine kallikrein and bovine trypsin, to identify the structural features underlying this functional diversity. The final rK9 model is structurally similar to rK2, but variable regions surrounding the active site differ quite markedly from the reference proteins. The kallikrein loop, which differs from that in porcine kallikrein by a seven-residue insertion, has been generated de novo and subjected to simulated annealing to assess its influence on the restricted substrate specificity of these proteinases. The proposed conformation of the specificity pocket in rK9 differs from that of other serine proteinases, but it can still accommodate both aromatic and basic amino acid side chains at the substra...Continue Reading

Citations

May 6, 1998·Protein Science : a Publication of the Protein Society·B A KatzE B Springman
Apr 2, 1999·European Journal of Biochemistry·H Czapinska, J Otlewski
Sep 5, 2014·Journal of Chemical Information and Modeling·Arben KojtariHai-Feng Ji

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