1gxd
From Proteopedia
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|PDB= 1gxd |SIZE=350|CAPTION= <scene name='initialview01'>1gxd</scene>, resolution 3.10Å | |PDB= 1gxd |SIZE=350|CAPTION= <scene name='initialview01'>1gxd</scene>, resolution 3.10Å | ||
|SITE= <scene name='pdbsite=S4A:Ca+Binding+Site+For+Chain+B'>S4A</scene> | |SITE= <scene name='pdbsite=S4A:Ca+Binding+Site+For+Chain+B'>S4A</scene> | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Gelatinase_A Gelatinase A], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.24 3.4.24.24] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Gelatinase_A Gelatinase A], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.24 3.4.24.24] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1gxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gxd OCA], [http://www.ebi.ac.uk/pdbsum/1gxd PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1gxd RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
Matrix metalloproteinases (MMPs) are a family of multidomain enzymes involved in the physiological degradation of connective tissue, as well as in pathological states such as tumor invasion and arthritis. Apart from transcriptional regulation, MMPs are controlled by proenzyme activation and a class of specific tissue inhibitors of metalloproteinases (TIMPs) that bind to the catalytic site. TIMP-2 is a potent inhibitor of MMPs, but it has also been implicated in a unique cell surface activation mechanism of latent MMP-2/gelatinase A/type IV collagenase (proMMP-2), through its binding to the hemopexin domain of proMMP-2 on the one hand and to a membrane-type MMP activator on the other. The present crystal structure of the human proMMP-2/TIMP-2 complex reveals an interaction between the hemopexin domain of proMMP-2 and the C-terminal domain of TIMP-2, leaving the catalytic site of MMP-2 and the inhibitory site of TIMP-2 distant and spatially isolated. The interfacial contact of these two proteins is characterized by two distinct binding regions composed of alternating hydrophobic and hydrophilic interactions. This unique structure provides information for how specificity for noninhibitory MMP/TIMP complex formation is achieved. | Matrix metalloproteinases (MMPs) are a family of multidomain enzymes involved in the physiological degradation of connective tissue, as well as in pathological states such as tumor invasion and arthritis. Apart from transcriptional regulation, MMPs are controlled by proenzyme activation and a class of specific tissue inhibitors of metalloproteinases (TIMPs) that bind to the catalytic site. TIMP-2 is a potent inhibitor of MMPs, but it has also been implicated in a unique cell surface activation mechanism of latent MMP-2/gelatinase A/type IV collagenase (proMMP-2), through its binding to the hemopexin domain of proMMP-2 on the one hand and to a membrane-type MMP activator on the other. The present crystal structure of the human proMMP-2/TIMP-2 complex reveals an interaction between the hemopexin domain of proMMP-2 and the C-terminal domain of TIMP-2, leaving the catalytic site of MMP-2 and the inhibitory site of TIMP-2 distant and spatially isolated. The interfacial contact of these two proteins is characterized by two distinct binding regions composed of alternating hydrophobic and hydrophilic interactions. This unique structure provides information for how specificity for noninhibitory MMP/TIMP complex formation is achieved. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Osteolysis, idiopathic, Saudi type OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=120360 120360]], Winchester syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=120360 120360]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Tryggvason, K.]] | [[Category: Tryggvason, K.]] | ||
[[Category: Tuuttila, A.]] | [[Category: Tuuttila, A.]] | ||
| - | [[Category: CA]] | ||
| - | [[Category: SO4]] | ||
| - | [[Category: ZN]] | ||
[[Category: collagen degradation]] | [[Category: collagen degradation]] | ||
[[Category: extracellular matrix]] | [[Category: extracellular matrix]] | ||
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[[Category: zymogen]] | [[Category: zymogen]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:53:16 2008'' |
Revision as of 17:53, 30 March 2008
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| , resolution 3.10Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | , , | ||||||
| Activity: | Gelatinase A, with EC number 3.4.24.24 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
PROMMP-2/TIMP-2 COMPLEX
Overview
Matrix metalloproteinases (MMPs) are a family of multidomain enzymes involved in the physiological degradation of connective tissue, as well as in pathological states such as tumor invasion and arthritis. Apart from transcriptional regulation, MMPs are controlled by proenzyme activation and a class of specific tissue inhibitors of metalloproteinases (TIMPs) that bind to the catalytic site. TIMP-2 is a potent inhibitor of MMPs, but it has also been implicated in a unique cell surface activation mechanism of latent MMP-2/gelatinase A/type IV collagenase (proMMP-2), through its binding to the hemopexin domain of proMMP-2 on the one hand and to a membrane-type MMP activator on the other. The present crystal structure of the human proMMP-2/TIMP-2 complex reveals an interaction between the hemopexin domain of proMMP-2 and the C-terminal domain of TIMP-2, leaving the catalytic site of MMP-2 and the inhibitory site of TIMP-2 distant and spatially isolated. The interfacial contact of these two proteins is characterized by two distinct binding regions composed of alternating hydrophobic and hydrophilic interactions. This unique structure provides information for how specificity for noninhibitory MMP/TIMP complex formation is achieved.
About this Structure
1GXD is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural insight into the complex formation of latent matrix metalloproteinase 2 with tissue inhibitor of metalloproteinase 2., Morgunova E, Tuuttila A, Bergmann U, Tryggvason K, Proc Natl Acad Sci U S A. 2002 May 28;99(11):7414-9. PMID:12032297
Page seeded by OCA on Sun Mar 30 20:53:16 2008
