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1buv

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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'''
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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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(as it appears on PubMed at http://www.pubmed.gov), where 9724659 is the PubMed ID number.
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{{ABSTRACT_PUBMED_9724659}}
==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]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 11:58:54 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 19:45:26 2008''

Revision as of 16:45, 30 June 2008

Template:STRUCTURE 1buv

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

Template:ABSTRACT PUBMED 9724659

About this Structure

1BUV is a Protein complex structure of sequences from Bos taurus and Homo sapiens. 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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