1eub: Difference between revisions

Revision as of 15:31, 2 May 2008

SOLUTION STRUCTURE OF THE CATALYTIC DOMAIN OF HUMAN COLLAGENASE-3 (MMP-13) COMPLEXED TO A POTENT NON-PEPTIDIC SULFONAMIDE INHIBITOR

OverviewOverview

The full three-dimensional structure of the catalytic domain of human collagenase-3 (MMP-13) complexed to a potent, sulfonamide hydroxamic acid inhibitor (CGS 27023) has been determined by NMR spectroscopy. The results reveal a core domain for the protein consisting of three alpha-helices and five beta-sheet strands with an overall tertiary fold similar to the catalytic domains of other matrix metalloproteinase family members. The S1' pocket, which is the major site of hydrophobic binding interaction, was found to be a wide cleft spanning the length of the protein and presenting facile opportunity for inhibitor extension deep into the pocket. Comparison with the reported X-ray structure of collagenase-3 showed evidence of flexibility for the loop region flanking the S1' pocket in both NMR and X-ray data. This flexibility was corroborated by NMR dynamics studies. Inhibitor binding placed the methoxy phenyl ring in the S1' pocket with the remainder of the molecule primarily solvent-exposed. The binding mode for this inhibitor was found to be similar with respect to stromelysin-1 and collagenase-1; however, subtle comparative differences in the interactions between inhibitor and enzyme were observed for the three MMPs that were consistent with their respective binding potencies.

About this StructureAbout this Structure

1EUB is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Solution structure of the catalytic domain of human collagenase-3 (MMP-13) complexed to a potent non-peptidic sulfonamide inhibitor: binding comparison with stromelysin-1 and collagenase-1., Zhang X, Gonnella NC, Koehn J, Pathak N, Ganu V, Melton R, Parker D, Hu SI, Nam KY, J Mol Biol. 2000 Aug 11;301(2):513-24. PMID:10926524 Page seeded by OCA on Fri May 2 15:31:24 2008

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OCA

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 [[Image:1eub.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1eub |SIZE=350|CAPTION= <scene name='initialview01'>1eub</scene>
+The line below this paragraph, containing "STRUCTURE_1eub", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=3MP:3-METHYLPYRIDINE'>3MP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=HAV:HYDROXYAMINOVALINE'>HAV</scene>, <scene name='pdbligand=MSB:1-METHYLOXY-4-SULFONE-BENZENE'>MSB</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY=
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_1eub|  PDB=1eub  |  SCENE=  }}
-|RELATEDENTRY=[[456c|456C]], [[830c|830C]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1eub FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1eub OCA], [http://www.ebi.ac.uk/pdbsum/1eub PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1eub RCSB]</span>
-}}
 '''SOLUTION STRUCTURE OF THE CATALYTIC DOMAIN OF HUMAN COLLAGENASE-3 (MMP-13) COMPLEXED TO A POTENT NON-PEPTIDIC SULFONAMIDE INHIBITOR'''
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 [[Category: Pathak, N.]]
 [[Category: Zhang, X.]]
-[[Category: alpha helix]]
+[[Category: Alpha helix]]
-[[Category: beta sheet]]
+[[Category: Beta sheet]]
-[[Category: protein-inhibitor complex]]
+[[Category: Protein-inhibitor complex]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 15:31:24 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:09:47 2008''