1buv: Difference between revisions
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==Overview== | ==Overview== | ||
The proteolytic activity of matrix metalloproteinases (MMPs) towards | 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== | ==About this Structure== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Bode, W.]] | [[Category: Bode, W.]] | ||
[[Category: Calvete, J | [[Category: Calvete, J J.]] | ||
[[Category: Fernandez-Catalan, C.]] | [[Category: Fernandez-Catalan, C.]] | ||
[[Category: Huber, R.]] | [[Category: Huber, R.]] | ||
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[[Category: tissue inhibitor of metalloproteinases]] | [[Category: tissue inhibitor of metalloproteinases]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:59:21 2008'' | ||
Revision as of 09:59, 21 February 2008
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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
Page seeded by OCA on Thu Feb 21 11:59:21 2008
Proteopedia Page Contributors and Editors (what is this?)
- Pages with broken file links
- Bos taurus
- Homo sapiens
- Membrane-type matrix metalloproteinase-1
- Protein complex
- Bode, W.
- Calvete, J J.
- Fernandez-Catalan, C.
- Huber, R.
- Lichte, A.
- Maskos, K.
- Tschesche, H.
- Turk, D.
- CA
- ZN
- Crystal structure
- Matrix metalloproteinase
- Pro-gelatinase a activator
- Proteinase complex
- Tissue inhibitor of metalloproteinases
