1s2c
From Proteopedia
(New page: 200px<br /> <applet load="1s2c" size="450" color="white" frame="true" align="right" spinBox="true" caption="1s2c, resolution 1.80Å" /> '''Crystal structures ...) |
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caption="1s2c, resolution 1.80Å" /> | caption="1s2c, resolution 1.80Å" /> | ||
'''Crystal structures of prostaglandin D2 11-ketoreductase in complex with the non-steroidal anti-inflammatory drugs flufenamic acid and indomethacin'''<br /> | '''Crystal structures of prostaglandin D2 11-ketoreductase in complex with the non-steroidal anti-inflammatory drugs flufenamic acid and indomethacin'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1S2C is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAP, FLF and DMS as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1S2C is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAP:'>NAP</scene>, <scene name='pdbligand=FLF:'>FLF</scene> and <scene name='pdbligand=DMS:'>DMS</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S2C OCA]. |
==Reference== | ==Reference== | ||
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[[Category: tim-barrel]] | [[Category: tim-barrel]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:51:44 2008'' |
Revision as of 14:51, 15 February 2008
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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 with , and as ligands. 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
Page seeded by OCA on Fri Feb 15 16:51:44 2008
Categories: Homo sapiens | Single protein | Bunce, C.M. | Cummings, S.M. | Desmond, J.C. | Lovering, A.L. | Ride, J.P. | White, S.A. | DMS | FLF | NAP | Tim-barrel
