1hov

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SOLUTION STRUCTURE OF A CATALYTIC DOMAIN OF MMP-2 COMPLEXED WITH SC-74020

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

MMP-2 is a member of the matrix metalloproteinase family that has been, implicated in tumor cell metastasis and angiogenesis. Here, we describe, the solution structure of a catalytic domain of MMP-2 complexed with a, hydroxamic acid inhibitor (SC-74020), determined by three-dimensional, heteronuclear NMR spectroscopy. The catalytic domain, designated MMP-2C, has a short peptide linker replacing the internal fibronectin-domain, insertion and is enzymatically active. Distance geometry-simulated, annealing calculations yielded 14 converged structures with atomic, root-mean-square deviations (r.m.s.d.) of 1.02 and 1.62 A from the mean, coordinate positions for the backbone and for all heavy atoms, respectively, when 11 residues at the N-terminus are excluded. The, structure has the same global fold as observed for other MMP catalytic, domains and is similar to previously solved crystal structures of MMP-2., Differences observed between the solution and the crystal structures, near, the bottom of the S1' specificity loop, appear to be induced by the large, inhibitor present in the solution structure. The MMP-2C solution structure, is compared with MMP-8 crystal structure bound to the same inhibitor to, highlight the differences especially in the S1' specificity loop. The, finding provides a structural explanation for the selectivity between, MMP-2 and MMP-8 that is achieved by large inhibitors.

Disease

Known diseases associated with this structure: Osteolysis, idiopathic, Saudi type OMIM:[120360], Winchester syndrome OMIM:[120360]

About this Structure

1HOV is a Single protein structure of sequence from Homo sapiens with ZN, CA and I52 as ligands. Active as Gelatinase A, with EC number 3.4.24.24 Full crystallographic information is available from OCA.

Reference

Solution structure and backbone dynamics of the catalytic domain of matrix metalloproteinase-2 complexed with a hydroxamic acid inhibitor., Feng Y, Likos JJ, Zhu L, Woodward H, Munie G, McDonald JJ, Stevens AM, Howard CP, De Crescenzo GA, Welsch D, Shieh HS, Stallings WC, Biochim Biophys Acta. 2002 Jul 29;1598(1-2):10-23. PMID:12147339

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