966c
From Proteopedia
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|PDB= 966c |SIZE=350|CAPTION= <scene name='initialview01'>966c</scene>, resolution 1.9Å | |PDB= 966c |SIZE=350|CAPTION= <scene name='initialview01'>966c</scene>, resolution 1.9Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=RS2:N-HYDROXY-2-[4-(4-PHENOXY-BENZENESULFONYL)-TETRAHYDRO-PYRAN-4-YL]-ACETAMIDE'>RS2</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=966c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=966c OCA], [http://www.ebi.ac.uk/pdbsum/966c PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=966c RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
The X-ray crystal structures of the catalytic domain of human collagenase-3 (MMP-13) and collagenase-1 (MMP-1) with bound inhibitors provides a basis for understanding the selectivity profile of a novel series of matrix metalloprotease (MMP) inhibitors. Differences in the relative size and shape of the MMP S1' pockets suggest that this pocket is a critical determinant of MMP inhibitor selectivity. The collagenase-3 S1' pocket is long and open, easily accommodating large P1' groups, such as diphenylether. In contrast, the collagenase-1 S1' pocket must undergo a conformational change to accommodate comparable P1' groups. The selectivity of the diphenylether series of inhibitors for collagenase-3 is largely determined by their affinity for the preformed S1' pocket of collagenase-3, as compared to the induced fit in collagenase-1. | The X-ray crystal structures of the catalytic domain of human collagenase-3 (MMP-13) and collagenase-1 (MMP-1) with bound inhibitors provides a basis for understanding the selectivity profile of a novel series of matrix metalloprotease (MMP) inhibitors. Differences in the relative size and shape of the MMP S1' pockets suggest that this pocket is a critical determinant of MMP inhibitor selectivity. The collagenase-3 S1' pocket is long and open, easily accommodating large P1' groups, such as diphenylether. In contrast, the collagenase-1 S1' pocket must undergo a conformational change to accommodate comparable P1' groups. The selectivity of the diphenylether series of inhibitors for collagenase-3 is largely determined by their affinity for the preformed S1' pocket of collagenase-3, as compared to the induced fit in collagenase-1. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: COPD, rate of decline of lung function in OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=120353 120353]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Wart, H Van.]] | [[Category: Wart, H Van.]] | ||
[[Category: Welch, A.]] | [[Category: Welch, A.]] | ||
| - | [[Category: CA]] | ||
| - | [[Category: RS2]] | ||
| - | [[Category: ZN]] | ||
[[Category: matrix metalloprotease]] | [[Category: matrix metalloprotease]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:45:53 2008'' |
Revision as of 02:45, 31 March 2008
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| , resolution 1.9Å | |||||||
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| Ligands: | , , | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF FIBROBLAST COLLAGENASE-1 COMPLEXED TO A DIPHENYL-ETHER SULPHONE BASED HYDROXAMIC ACID
Overview
The X-ray crystal structures of the catalytic domain of human collagenase-3 (MMP-13) and collagenase-1 (MMP-1) with bound inhibitors provides a basis for understanding the selectivity profile of a novel series of matrix metalloprotease (MMP) inhibitors. Differences in the relative size and shape of the MMP S1' pockets suggest that this pocket is a critical determinant of MMP inhibitor selectivity. The collagenase-3 S1' pocket is long and open, easily accommodating large P1' groups, such as diphenylether. In contrast, the collagenase-1 S1' pocket must undergo a conformational change to accommodate comparable P1' groups. The selectivity of the diphenylether series of inhibitors for collagenase-3 is largely determined by their affinity for the preformed S1' pocket of collagenase-3, as compared to the induced fit in collagenase-1.
About this Structure
966C is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structures of MMP-1 and -13 reveal the structural basis for selectivity of collagenase inhibitors., Lovejoy B, Welch AR, Carr S, Luong C, Broka C, Hendricks RT, Campbell JA, Walker KA, Martin R, Van Wart H, Browner MF, Nat Struct Biol. 1999 Mar;6(3):217-21. PMID:10074939
Page seeded by OCA on Mon Mar 31 05:45:53 2008
