2rdl

From Proteopedia

Revision as of 06:13, 13 February 2008

Hamster Chymase 2

Overview

Divergence of substrate specificity within the context of a common, structural framework represents an important mechanism by which new enzyme, activity naturally evolves. We present enzymological and X-ray structural, data for hamster chymase-2 (HAM2) that provides a detailed explanation for, the unusual hydrolytic specificity of this rodent alpha-chymase. In, enzymatic characterization, hamster chymase-1 (HAM1) showed typical, chymase proteolytic activity. In contrast, HAM2 exhibited atypical, substrate specificity, cleaving on the carboxyl side of the P1 substrate, residues Ala and Val, characteristic of elastolytic rather than, chymotryptic specificity. The 2.5 A resolution crystal structure of HAM2, complexed to the peptidyl inhibitor, MeOSuc-Ala-Ala-Pro-Ala-chloromethylketone revealed a narrow and shallow S1, substrate binding pocket that accommodated only a small hydrophobic, residue (e.g. Ala or Val). The different substrate specificities of HAM2, and HAM1 are explained by changes in four S1 substrate site residues, (positions 189, 190, 216 and 226). Of these, Asn189, Val190 and Val216, form an easily identifiable triplet in all known rodent alpha-chymases, that can be used to predict elastolytic specificity for novel chymase-like, sequences. Phylogenetic comparison defines guinea pig and rabbit chymases, as the closest orthologs to rodent alpha-chymases.

About this Structure

2RDL is a Single protein structure of sequence from Mesocricetus auratus with as ligand. Known structural/functional Sites: , , , , and . Full crystallographic information is available from OCA.

Reference

Structural basis for elastolytic substrate specificity in rodent alpha -chymases., Kervinen J, Abad M, Crysler C, Kolpak M, Mahan AD, Masucci JA, Bayoumy S, Cummings MD, Yao X, Olson M, de Garavilla L, Kuo L, Deckman I, Spurlino J, J Biol Chem. 2007 Oct 31;. PMID:17981788

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