1b8y: Difference between revisions
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[[Image:1b8y.jpg|left|200px]] | [[Image:1b8y.jpg|left|200px]] | ||
'''X-RAY STRUCTURE OF HUMAN STROMELYSIN CATALYTIC DOMAIN COMPLEXED WITH NON-PEPTIDE INHIBITORS: IMPLICATIONS FOR INHIBITOR SELECTIVITY''' | {{Structure | ||
|PDB= 1b8y |SIZE=350|CAPTION= <scene name='initialview01'>1b8y</scene>, resolution 2.0Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=IN7:[4-(4-PHENYL-PIPERIDIN-1-YL)-BENZENESULFONYLAMINO]-ACETIC ACID'>IN7</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Stromelysin_1 Stromelysin 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.17 3.4.24.17] | |||
|GENE= | |||
}} | |||
'''X-RAY STRUCTURE OF HUMAN STROMELYSIN CATALYTIC DOMAIN COMPLEXED WITH NON-PEPTIDE INHIBITORS: IMPLICATIONS FOR INHIBITOR SELECTIVITY''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1B8Y is a [ | 1B8Y is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B8Y OCA]. | ||
==Reference== | ==Reference== | ||
X-ray structure of human stromelysin catalytic domain complexed with nonpeptide inhibitors: implications for inhibitor selectivity., Pavlovsky AG, Williams MG, Ye QZ, Ortwine DF, Purchase CF 2nd, White AD, Dhanaraj V, Roth BD, Johnson LL, Hupe D, Humblet C, Blundell TL, Protein Sci. 1999 Jul;8(7):1455-62. PMID:[http:// | X-ray structure of human stromelysin catalytic domain complexed with nonpeptide inhibitors: implications for inhibitor selectivity., Pavlovsky AG, Williams MG, Ye QZ, Ortwine DF, Purchase CF 2nd, White AD, Dhanaraj V, Roth BD, Johnson LL, Hupe D, Humblet C, Blundell TL, Protein Sci. 1999 Jul;8(7):1455-62. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10422833 10422833] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: stromelysin-1]] | [[Category: stromelysin-1]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:07:51 2008'' | ||
Revision as of 11:07, 20 March 2008
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| , resolution 2.0Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , and | ||||||
| Activity: | Stromelysin 1, with EC number 3.4.24.17 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
X-RAY STRUCTURE OF HUMAN STROMELYSIN CATALYTIC DOMAIN COMPLEXED WITH NON-PEPTIDE INHIBITORS: IMPLICATIONS FOR INHIBITOR SELECTIVITY
OverviewOverview
Effective inhibitors of matrix metalloproteinases (MMPs), a family of connective tissue-degrading enzymes, could be useful for the treatment of diseases such as cancer, multiple sclerosis, and arthritis. Many of the known MMP inhibitors are derived from peptide substrates, with high potency in vitro but little selectivity among MMPs and poor bioavailability. We have discovered nonpeptidic MMP inhibitors with improved properties, and report here the crystal structures of human stromelysin-1 catalytic domain (SCD) complexed with four of these inhibitors. The structures were determined and refined at resolutions ranging from 1.64 to 2.0 A. Each inhibitor binds in the active site of SCD such that a bulky diphenyl piperidine moiety penetrates a deep, predominantly hydrophobic S'1 pocket. The active site structure of the SCD is similar in all four inhibitor complexes, but differs substantially from the peptide hydroxamate complex, which has a smaller side chain bound in the S'1 pocket. The largest differences occur in the loop forming the "top" of this pocket. The occupation of these nonpeptidic inhibitors in the S'1 pocket provides a structural basis to explain their selectivity among MMPs. An analysis of the unique binding mode predicts structural modifications to design improved MMP inhibitors.
DiseaseDisease
Known diseases associated with this structure: Coronary heart disease, susceptibility to OMIM:[185250]
About this StructureAbout this Structure
1B8Y is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
X-ray structure of human stromelysin catalytic domain complexed with nonpeptide inhibitors: implications for inhibitor selectivity., Pavlovsky AG, Williams MG, Ye QZ, Ortwine DF, Purchase CF 2nd, White AD, Dhanaraj V, Roth BD, Johnson LL, Hupe D, Humblet C, Blundell TL, Protein Sci. 1999 Jul;8(7):1455-62. PMID:10422833
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