1s2c
From Proteopedia
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|PDB= 1s2c |SIZE=350|CAPTION= <scene name='initialview01'>1s2c</scene>, resolution 1.80Å | |PDB= 1s2c |SIZE=350|CAPTION= <scene name='initialview01'>1s2c</scene>, resolution 1.80Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=FLF:2-[[3-(TRIFLUOROMETHYL)PHENYL]AMINO]+BENZOIC+ACID'>FLF</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1s1p|1S1P]], [[1s1r|1S1R]], [[1s2a|1S2A]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1s2c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s2c OCA], [http://www.ebi.ac.uk/pdbsum/1s2c PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1s2c RCSB]</span> | ||
}} | }} | ||
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[[Category: Ride, J P.]] | [[Category: Ride, J P.]] | ||
[[Category: White, S A.]] | [[Category: White, S A.]] | ||
| - | [[Category: DMS]] | ||
| - | [[Category: FLF]] | ||
| - | [[Category: NAP]] | ||
[[Category: tim-barrel]] | [[Category: tim-barrel]] | ||
| - | ''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 23:36:23 2008'' |
Revision as of 20:36, 30 March 2008
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| , resolution 1.80Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Related: | 1S1P, 1S1R, 1S2A
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structures of prostaglandin D2 11-ketoreductase in complex with the non-steroidal anti-inflammatory drugs flufenamic acid and indomethacin
Overview
It is becoming increasingly well established that nonsteroidal anti-inflammatory drugs (NSAID) protect against tumors of the gastrointestinal tract and that they may also protect against a variety of other tumors. These activities have been widely attributed to the inhibition of cylooxygenases (COX) and, in particular, COX-2. However, several observations have indicated that other targets may be involved. Besides targeting COX, certain NSAID also inhibit enzymes belonging to the aldo-keto reductase (AKR) family, including AKR1C3. We have demonstrated previously that overexpression of AKR1C3 acts to suppress cell differentiation and promote proliferation in myeloid cells. However, this enzyme has a broad tissue distribution and therefore represents a novel candidate for the target of the COX-independent antineoplastic actions of NSAID. Here we report on the X-ray crystal structures of AKR1C3 complexed with the NSAID indomethacin (1.8 A resolution) or flufenamic acid (1.7 A resolution). One molecule of indomethacin is bound in the active site, whereas flufenamic acid binds to both the active site and the beta-hairpin loop, at the opposite end of the central beta-barrel. Two other crystal structures (1.20 and 2.1 A resolution) show acetate bound in the active site occupying the proposed oxyanion hole. The data underline AKR1C3 as a COX-independent target for NSAID and will provide a structural basis for the future development of new cancer therapies with reduced COX-dependent side effects.
About this Structure
1S2C is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structures of prostaglandin D(2) 11-ketoreductase (AKR1C3) in complex with the nonsteroidal anti-inflammatory drugs flufenamic acid and indomethacin., Lovering AL, Ride JP, Bunce CM, Desmond JC, Cummings SM, White SA, Cancer Res. 2004 Mar 1;64(5):1802-10. PMID:14996743
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