1uea

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spinqualitylabelsall models 1uea, resolution 2.8Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

MMP-3/TIMP-1 COMPLEX

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

Matrix metalloproteinases (MMPs) are zinc endopeptidases that are required, for the degradation of extracellular matrix components during normal, embryo development, morphogenesis and tissue remodelling. Their, proteolytic activities are precisely regulated by endogenous tissue, inhibitors of metalloproteinases (TIMPs). Disruption of this balance, results in diseases such as arthritis, atherosclerosis, tumour growth and, metastasis. Here we report the crystal structure of an MMP-TIMP complex, formed between the catalytic domain of human stromelysin-1 (MMP-3) and, human TIMP-1. TIMP-1, a 184-residue protein, has the shape of an, elongated, contiguous wedge. With its long edge, consisting of five, different chain regions, it occupies the entire length of the active-site, cleft of MMP-3. The central disulphide-linked segments Cys 1-Thr 2-Cys, 3-Val 4 and Ser 68-Val 69 bind to either side of the catalytic zinc. Cys 1, bidentally coordinates this zinc, and the Thr-2 side chain extends into, the large specificity pocket of MMP-3. This unusual architecture of the, interface between MMP-3 and TIMP-1 suggests new possibilities for, designing TIMP variants and synthetic MMP inhibitors with potential, therapeutic applications.

Disease

Known diseases associated with this structure: Coronary heart disease, susceptibility to OMIM:[185250], Sorsby fundus dystrophy OMIM:[188826]

About this Structure

1UEA is a Protein complex structure of sequences from Homo sapiens with and as ligands. Active as Stromelysin 1, with EC number 3.4.24.17 Full crystallographic information is available from OCA.

Reference

Mechanism of inhibition of the human matrix metalloproteinase stromelysin-1 by TIMP-1., Gomis-Ruth FX, Maskos K, Betz M, Bergner A, Huber R, Suzuki K, Yoshida N, Nagase H, Brew K, Bourenkov GP, Bartunik H, Bode W, Nature. 1997 Sep 4;389(6646):77-81. PMID:9288970

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