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spinqualitylabelsall models 1buv, resolution 2.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

CRYSTAL STRUCTURE OF THE MT1-MMP-TIMP-2 COMPLEX

Overview

The proteolytic activity of matrix metalloproteinases (MMPs) towards, extracellular matrix components is held in check by the tissue inhibitors, of metalloproteinases (TIMPs). The binary complex of TIMP-2 and, membrane-type-1 MMP (MT1-MMP) forms a cell surface located 'receptor', involved in pro-MMP-2 activation. We have solved the 2.75 A crystal, structure of the complex between the catalytic domain of human MT1-MMP, (cdMT1-MMP) and bovine TIMP-2. In comparison with our previously, determined MMP-3-TIMP-1 complex, both proteins are considerably tilted to, one another and show new features. CdMT1-MMP, apart from exhibiting the, classical MMP fold, displays two large insertions remote from the, active-site cleft that might be important for interaction with, macromolecular substrates. The TIMP-2 polypeptide chain, as in TIMP-1, folds into a continuous wedge; the A-B edge loop is much more elongated, and tilted, however, wrapping around the S-loop and the beta-sheet rim of, the MT1-MMP. In addition, both C-terminal edge loops make more, interactions with the target enzyme. The C-terminal acidic tail of TIMP-2, is disordered but might adopt a defined structure upon binding to, pro-MMP-2; the Ser2 side-chain of TIMP-2 extends into the voluminous S1', specificity pocket of cdMT1-MMP, with its Ogamma pointing towards the, carboxylate of the catalytic Glu240. The lower affinity of TIMP-1 for, MT1-MMP compared with TIMP-2 might be explained by a reduced number of, favourable interactions.

About this Structure

1BUV is a Protein complex structure of sequences from Bos taurus and Homo sapiens with CA and ZN as ligands. Active as Membrane-type matrix metalloproteinase-1, with EC number 3.4.24.80 Full crystallographic information is available from OCA.

Reference

Crystal structure of the complex formed by the membrane type 1-matrix metalloproteinase with the tissue inhibitor of metalloproteinases-2, the soluble progelatinase A receptor., Fernandez-Catalan C, Bode W, Huber R, Turk D, Calvete JJ, Lichte A, Tschesche H, Maskos K, EMBO J. 1998 Sep 1;17(17):5238-48. PMID:9724659

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