View source for 1s1r

[[Image:1s1r.gif|left|200px]]

 {{Structure
|PDB= 1s1r |SIZE=350|CAPTION= <scene name='initialview01'>1s1r</scene>, resolution 2.00&Aring;
|SITE= 
|LIGAND= <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>
|ACTIVITY= 
|GENE= 
|DOMAIN=
|RELATEDENTRY=[[1s1p|1S1P]], [[1s2a|1S2A]], [[1s2c|1S2C]]
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1s1r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s1r OCA], [http://www.ebi.ac.uk/pdbsum/1s1r PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1s1r RCSB]</span>
}}

'''Crystal structures of prostaglandin D2 11-ketoreductase (AKR1C3) 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==
1S1R 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=1S1R 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:[http://www.ncbi.nlm.nih.gov/pubmed/14996743 14996743]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Bunce, C M.]]
[[Category: Cummings, S M.]]
[[Category: Desmond, J C.]]
[[Category: Lovering, A L.]]
[[Category: Ride, J P.]]
[[Category: White, S A.]]
[[Category: tim-barrel]]

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