1eub
SOLUTION STRUCTURE OF THE CATALYTIC DOMAIN OF HUMAN COLLAGENASE-3 (MMP-13) COMPLEXED TO A POTENT NON-PEPTIDIC SULFONAMIDE INHIBITOR
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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 with ZN, CA, HAV, 3MP and MSB as ligands. 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
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