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| [[Image:1bqq.gif|left|200px]] | | [[Image:1bqq.gif|left|200px]] |
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| |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1bqq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bqq OCA], [http://www.ebi.ac.uk/pdbsum/1bqq PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1bqq RCSB]</span>
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| '''CRYSTAL STRUCTURE OF THE MT1-MMP--TIMP-2 COMPLEX''' | | '''''' |
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| ==Overview==
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| 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.
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| ==About this Structure== | | ==About this Structure== |
| 1BQQ is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BQQ OCA].
| | Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. |
| | | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 11:50:35 2008'' |
| ==Reference==
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| 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:[http://www.ncbi.nlm.nih.gov/pubmed/9724659 9724659]
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| [[Category: Bos taurus]]
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| [[Category: Homo sapiens]]
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| [[Category: Protein complex]]
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| [[Category: Bode, W.]]
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| [[Category: Calvete, J J.]]
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| [[Category: Fernandez-Catalan, C.]]
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| [[Category: Huber, R.]]
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| [[Category: Lichte, A.]]
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| [[Category: Maskos, K.]]
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| [[Category: Tschesche, H.]]
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| [[Category: Turk, D.]]
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| [[Category: Crystal structure]]
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| [[Category: Matrix metalloproteinase]]
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| [[Category: Pro-gelatinase a activator]]
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| [[Category: Proteinase complex]]
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| [[Category: Tissue inhibitor of metalloproteinase]]
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| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Apr 7 20:42:48 2008'' | |