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| [[Image:1buv.jpg|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_1buv| PDB=1buv | SCENE= }} | | {{STRUCTURE_1buv| PDB=1buv | SCENE= }} |
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| '''CRYSTAL STRUCTURE OF THE MT1-MMP-TIMP-2 COMPLEX'''
| | ===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. | | The line below this paragraph, {{ABSTRACT_PUBMED_9724659}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 9724659 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_9724659}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Proteinase complex]] | | [[Category: Proteinase complex]] |
| [[Category: Tissue inhibitor of metalloproteinase]] | | [[Category: Tissue inhibitor of metalloproteinase]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 11:58:54 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 19:45:26 2008'' |
