1fls

From Proteopedia

Revision as of 13:48, 15 February 2008

SOLUTION STRUCTURE OF THE CATALYTIC FRAGMENT OF HUMAN COLLAGENASE-3 (MMP-13) COMPLEXED WITH A HYDROXAMIC ACID INHIBITOR

Overview

The high-resolution solution structure of the catalytic fragment of human, collagenase-3 (MMP-13) complexed with a sulfonamide derivative of a, hydroxamic acid compound (WAY-151693) has been determined by, multidimensional heteronuclear NMR. A total of 30 structures were, calculated for residues 7-164 by means of hybrid distance, geometry-simulated annealing using a total of 3280 experimental NMR, restraints. The atomic rms distribution about the mean coordinate, positions for the 30 structures is 0.43(+/-0.05) A for the backbone atoms, 0.80(+/-0.09) A for all atoms, and 0.47(+/-0.04) A for all atoms excluding, disordered side-chains. The overall structure of MMP-13 is composed of a, beta-sheet consisting of five beta-strands in a mixed parallel and, anti-parallel arrangement and three alpha-helices where its overall fold, is consistent with previously solved MMP structures. A comparison of the, NMR structure of MMP-13 with the published 1.6 A resolution X-ray, structure indicates that the major differences between the structures is, associated with loop dynamics and crystal-packing interactions. The, side-chains of some active-site residues for the NMR and X-ray structures, of MMP-13 adopt distinct conformations. This is attributed to the presence, of unique inhibitors in the two structures that encounter distinct, interactions with MMP-13. The major structural difference observed between, the MMP-13 and MMP-1 NMR structures is the relative size and shape of the, S1' pocket where this pocket is significantly longer for MMP-13, nearly, reaching the surface of the protein. Additionally, MMP-1 and MMP-13, exhibit different dynamic properties for the active-site loop and the, structural Zn-binding region. The inhibitor WAY-151693 is well defined in, the MMP-13 active-site based on a total of 52 distance restraints. The, binding motif of WAY-151693 in the MMP-13 complex is consistent with our, previously reported MMP-1:CGS-27023A NMR structure and is similar to the, MMP-13: RS-130830 X-ray structure.

About this Structure

1FLS is a Single protein structure of sequence from Homo sapiens with , and as ligands. Full crystallographic information is available from OCA.

Reference

High-resolution solution structure of the catalytic fragment of human collagenase-3 (MMP-13) complexed with a hydroxamic acid inhibitor., Moy FJ, Chanda PK, Chen JM, Cosmi S, Edris W, Levin JI, Powers R, J Mol Biol. 2000 Sep 22;302(3):671-89. PMID:10986126

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