1eub: Difference between revisions
New page: left|200px<br /> <applet load="1eub" size="450" color="white" frame="true" align="right" spinBox="true" caption="1eub" /> '''SOLUTION STRUCTURE OF THE CATALYTIC DOMAIN ... |
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'''SOLUTION STRUCTURE OF THE CATALYTIC DOMAIN OF HUMAN COLLAGENASE-3 (MMP-13) COMPLEXED TO A POTENT NON-PEPTIDIC SULFONAMIDE INHIBITOR'''<br /> | '''SOLUTION STRUCTURE OF THE CATALYTIC DOMAIN OF HUMAN COLLAGENASE-3 (MMP-13) COMPLEXED TO A POTENT NON-PEPTIDIC SULFONAMIDE INHIBITOR'''<br /> | ||
==Overview== | ==Overview== | ||
The full three-dimensional structure of the catalytic domain of human | 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 Structure== | ==About this Structure== | ||
1EUB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN, CA, HAV, 3MP and MSB as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | 1EUB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=HAV:'>HAV</scene>, <scene name='pdbligand=3MP:'>3MP</scene> and <scene name='pdbligand=MSB:'>MSB</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EUB OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Ganu, V.]] | [[Category: Ganu, V.]] | ||
[[Category: Gonnella, N | [[Category: Gonnella, N C.]] | ||
[[Category: Hu, S | [[Category: Hu, S I.]] | ||
[[Category: Koehn, J.]] | [[Category: Koehn, J.]] | ||
[[Category: Melton, R.]] | [[Category: Melton, R.]] | ||
[[Category: Nam, K | [[Category: Nam, K Y.]] | ||
[[Category: Parker, D.]] | [[Category: Parker, D.]] | ||
[[Category: Pathak, N.]] | [[Category: Pathak, N.]] | ||
| Line 32: | Line 31: | ||
[[Category: protein-inhibitor complex]] | [[Category: protein-inhibitor complex]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:31:34 2008'' | ||
Revision as of 13:31, 21 February 2008
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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 with , , , and 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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