From Proteopedia
(Difference between revisions)
proteopedia linkproteopedia link
|
|
| Line 1: |
Line 1: |
| - | [[Image:1s2c.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:1s2c.png|left|200px]] |
| | | | |
| | <!-- | | <!-- |
| Line 9: |
Line 10: |
| | {{STRUCTURE_1s2c| PDB=1s2c | SCENE= }} | | {{STRUCTURE_1s2c| PDB=1s2c | SCENE= }} |
| | | | |
| - | '''Crystal structures of prostaglandin D2 11-ketoreductase in complex with the non-steroidal anti-inflammatory drugs flufenamic acid and indomethacin'''
| + | ===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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_14996743}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 14996743 is the PubMed ID number. |
| | + | --> |
| | + | {{ABSTRACT_PUBMED_14996743}} |
| | | | |
| | ==About this Structure== | | ==About this Structure== |
| Line 29: |
Line 33: |
| | [[Category: White, S A.]] | | [[Category: White, S A.]] |
| | [[Category: Tim-barrel]] | | [[Category: Tim-barrel]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 08:12:35 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 09:01:16 2008'' |
Revision as of 06:01, 29 July 2008
Template:STRUCTURE 1s2c
Crystal structures of prostaglandin D2 11-ketoreductase in complex with the non-steroidal anti-inflammatory drugs flufenamic acid and indomethacin
Template:ABSTRACT PUBMED 14996743
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
Page seeded by OCA on Tue Jul 29 09:01:16 2008
