1you
From Proteopedia
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|PDB= 1you |SIZE=350|CAPTION= <scene name='initialview01'>1you</scene>, resolution 2.30Å | |PDB= 1you |SIZE=350|CAPTION= <scene name='initialview01'>1you</scene>, resolution 2.30Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PFD:5-(2-ETHOXYETHYL)-5-[4-(4-FLUOROPHENOXY)PHENOXY]PYRIMIDINE-2,4,6(1H,3H,5H)-TRIONE'>PFD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= MMP13 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= MMP13 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1you FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1you OCA], [http://www.ebi.ac.uk/pdbsum/1you PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1you RCSB]</span> | ||
}} | }} | ||
| Line 23: | Line 26: | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Pandit, J.]] | [[Category: Pandit, J.]] | ||
| - | [[Category: CA]] | ||
| - | [[Category: PFD]] | ||
| - | [[Category: SO4]] | ||
| - | [[Category: ZN]] | ||
[[Category: hydrolase]] | [[Category: hydrolase]] | ||
[[Category: metalloprotease]] | [[Category: metalloprotease]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:15:54 2008'' |
Revision as of 22:15, 30 March 2008
| |||||||
| , resolution 2.30Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , | ||||||
| Gene: | MMP13 (Homo sapiens) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of the catalytic domain of MMP-13 complexed with a potent pyrimidinetrione inhibitor
Overview
Through the use of computational modeling, a series of pyrimidinetrione-based inhibitors of MMP-13 was designed based on a lead inhibitor identified through file screening. Incorporation of a biaryl ether moiety at the C-5 position of the pyrimidinetrione ring resulted in a dramatic enhancement of MMP-13 potency. Protein crystallography revealed that this moiety binds in the S(1)(') pocket of the enzyme. Optimization of the C-4 substituent of the terminal aromatic ring led to incorporation of selectivity versus MMP-14 (MT-1 MMP). Structure activity relationships of the biaryl ether substituent are presented as is pharmacokinetic data for a compound that meets our in vitro potency and selectivity goals.
About this Structure
1YOU is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Potent pyrimidinetrione-based inhibitors of MMP-13 with enhanced selectivity over MMP-14., Blagg JA, Noe MC, Wolf-Gouveia LA, Reiter LA, Laird ER, Chang SP, Danley DE, Downs JT, Elliott NC, Eskra JD, Griffiths RJ, Hardink JR, Haugeto AI, Jones CS, Liras JL, Lopresti-Morrow LL, Mitchell PG, Pandit J, Robinson RP, Subramanyam C, Vaughn-Bowser ML, Yocum SA, Bioorg Med Chem Lett. 2005 Apr 1;15(7):1807-10. PMID:15780611
Page seeded by OCA on Mon Mar 31 01:15:54 2008
