2dm6
From Proteopedia
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| - | [[Image:2dm6.gif|left|200px]]<br /><applet load="2dm6" size="350" color="white" frame="true" align="right" spinBox="true" | ||
| - | caption="2dm6, resolution 2.000Å" /> | ||
| - | '''Crystal structure of anti-configuration of indomethacin and leukotriene B4 12-hydroxydehydrogenase/15-oxo-prostaglandin 13-reductase complex'''<br /> | ||
| - | == | + | ==Crystal structure of anti-configuration of indomethacin and leukotriene B4 12-hydroxydehydrogenase/15-oxo-prostaglandin 13-reductase complex== |
| + | <StructureSection load='2dm6' size='340' side='right'caption='[[2dm6]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2dm6]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Cavia_porcellus Cavia porcellus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DM6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2DM6 FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IMN:INDOMETHACIN'>IMN</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=TAM:TRIS(HYDROXYETHYL)AMINOMETHANE'>TAM</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2dm6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2dm6 OCA], [https://pdbe.org/2dm6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2dm6 RCSB], [https://www.ebi.ac.uk/pdbsum/2dm6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2dm6 ProSAT], [https://www.topsan.org/Proteins/RSGI/2dm6 TOPSAN]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/PTGR1_CAVPO PTGR1_CAVPO] Functions as 15-oxo-prostaglandin 13-reductase and acts on 15-oxo-PGE1, 15-oxo-PGE2 and 15-oxo-PGE2-alpha. Catalyzes the conversion of leukotriene B4 into its biologically less active metabolite, 12-oxo-leukotriene B4. This is an initial and key step of metabolic inactivation of leukotriene B4. | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dm/2dm6_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2dm6 ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
The crystal structure of the ternary complex of leukotriene B4 12-hydroxydehydrogenase/15-oxo-prostaglandin (15-oxo-PG) 13-reductase (LTB4 12HD/PGR), an essential enzyme for eicosanoid inactivation pathways, with indomethacin and NADP+ has been solved. An indomethacin molecule bound in the anti-configuration at one of the two active site clefts of the homo-dimer interface in the LTB4 12HD/PGR and was confirmed by a binding calorimetry. The chlorobenzene ring is buried in the hydrophobic pore used as a binding site by the omega-chain of 15-oxo-PGE2. The carboxyl group interacts with the guanidino group of Arg56 and the phenolic hydroxyl group of Tyr262. Indomethacin shows a broad spectrum of efficacy against lipid-mediator related proteins including cyclooxygenase-2, phospholipase A2, PGF synthase and PGE synthase-2 but in the syn-configuration as well as LTB4 12HD/PGR in the anti-configuration. Indomethacin does not necessarily mimic the binding mode of the lipid-mediator substrates in the active sites of these complex structures. Thus, the broad spectrum of indomethacin efficacy can be attributed to its ability to adopt a range of different stable conformations. This allows the indomethacin to adapt to the distinct binding site features of each protein whilst maintaining favorable interactions between the carboxyl group and a counter charged functional group. | The crystal structure of the ternary complex of leukotriene B4 12-hydroxydehydrogenase/15-oxo-prostaglandin (15-oxo-PG) 13-reductase (LTB4 12HD/PGR), an essential enzyme for eicosanoid inactivation pathways, with indomethacin and NADP+ has been solved. An indomethacin molecule bound in the anti-configuration at one of the two active site clefts of the homo-dimer interface in the LTB4 12HD/PGR and was confirmed by a binding calorimetry. The chlorobenzene ring is buried in the hydrophobic pore used as a binding site by the omega-chain of 15-oxo-PGE2. The carboxyl group interacts with the guanidino group of Arg56 and the phenolic hydroxyl group of Tyr262. Indomethacin shows a broad spectrum of efficacy against lipid-mediator related proteins including cyclooxygenase-2, phospholipase A2, PGF synthase and PGE synthase-2 but in the syn-configuration as well as LTB4 12HD/PGR in the anti-configuration. Indomethacin does not necessarily mimic the binding mode of the lipid-mediator substrates in the active sites of these complex structures. Thus, the broad spectrum of indomethacin efficacy can be attributed to its ability to adopt a range of different stable conformations. This allows the indomethacin to adapt to the distinct binding site features of each protein whilst maintaining favorable interactions between the carboxyl group and a counter charged functional group. | ||
| - | + | Crystal structure of anti-configuration of indomethacin and leukotriene B4 12-hydroxydehydrogenase/15-oxo-prostaglandin 13-reductase complex reveals the structural basis of broad spectrum indomethacin efficacy.,Hori T, Ishijima J, Yokomizo T, Ago H, Shimizu T, Miyano M J Biochem. 2006 Sep;140(3):457-66. Epub 2006 Aug 17. PMID:16916844<ref>PMID:16916844</ref> | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 2dm6" style="background-color:#fffaf0;"></div> | |
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| - | + | ==See Also== | |
| + | *[[Leukotriene B4 hydroxydehydrogenase|Leukotriene B4 hydroxydehydrogenase]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Cavia porcellus]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Ago H]] | ||
| + | [[Category: Hori T]] | ||
| + | [[Category: Ishijima J]] | ||
| + | [[Category: Miyano M]] | ||
| + | [[Category: Shimizu T]] | ||
| + | [[Category: Yokomizo T]] | ||
Current revision
Crystal structure of anti-configuration of indomethacin and leukotriene B4 12-hydroxydehydrogenase/15-oxo-prostaglandin 13-reductase complex
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Categories: Cavia porcellus | Large Structures | Ago H | Hori T | Ishijima J | Miyano M | Shimizu T | Yokomizo T
