1d8f: Difference between revisions
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|PDB= 1d8f |SIZE=350|CAPTION= <scene name='initialview01'>1d8f</scene>, resolution 2.4Å | |PDB= 1d8f |SIZE=350|CAPTION= <scene name='initialview01'>1d8f</scene>, resolution 2.4Å | ||
|SITE= | |SITE= | ||
|LIGAND= | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SPI:N-HYDROXY-1-(4-METHOXYPHENYL)SULFONYL-4-BENZYLOXYCARBONYL-PIPERAZINE-2-CARBOXAMIDE'>SPI</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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] | |ACTIVITY= <span class='plainlinks'>[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] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1cqr|1CQR]], [[1d5j|1D5J]], [[1d7x|1D7X]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1d8f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1d8f OCA], [http://www.ebi.ac.uk/pdbsum/1d8f PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1d8f RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
A new generation of cyclic matrix metalloproteinase (MMP) inhibitors derived from dl-piperazinecarboxylic acid has been described. The design involves: incorporation of hydroxamic acid as the bidentate chelating agent for catalytic Zn(2+), placement of a sulfonamide group at the 1N-position of the piperazine ring to fill the S1' pocket of the enzyme, and finally attachment of diverse functional groups at the 4N-position to optimize potency and peroral absorption. A unique combination of all three elements produced inhibitor 20 with high affinity for MMPs 1, 3, 9, and 13 (24, 18, 1.9, and 1.3 nM, respectively). X-ray crystallography data obtained for MMP-3 cocrystallized with 20 gave detailed information on key binding interactions defining an overall scaffold geometry for piperazine-based MMP inhibitors. | A new generation of cyclic matrix metalloproteinase (MMP) inhibitors derived from dl-piperazinecarboxylic acid has been described. The design involves: incorporation of hydroxamic acid as the bidentate chelating agent for catalytic Zn(2+), placement of a sulfonamide group at the 1N-position of the piperazine ring to fill the S1' pocket of the enzyme, and finally attachment of diverse functional groups at the 4N-position to optimize potency and peroral absorption. A unique combination of all three elements produced inhibitor 20 with high affinity for MMPs 1, 3, 9, and 13 (24, 18, 1.9, and 1.3 nM, respectively). X-ray crystallography data obtained for MMP-3 cocrystallized with 20 gave detailed information on key binding interactions defining an overall scaffold geometry for piperazine-based MMP inhibitors. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Snider, C E.]] | [[Category: Snider, C E.]] | ||
[[Category: Taiwo, Y O.]] | [[Category: Taiwo, Y O.]] | ||
[[Category: inhibited]] | [[Category: inhibited]] | ||
[[Category: mixed alpha beta structure]] | [[Category: mixed alpha beta structure]] | ||
[[Category: zinc protease]] | [[Category: zinc protease]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:36:39 2008'' | ||
