1buv | pdb_00001buv

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

File:1buv.gif

spinqualitylabelsall models 1buv, resolution 2.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D

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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