2dm6: Difference between revisions

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[[Image:2dm6.gif|left|200px]]


{{Structure
==Crystal structure of anti-configuration of indomethacin and leukotriene B4 12-hydroxydehydrogenase/15-oxo-prostaglandin 13-reductase complex==
|PDB= 2dm6 |SIZE=350|CAPTION= <scene name='initialview01'>2dm6</scene>, resolution 2.000&Aring;
<StructureSection load='2dm6' size='340' side='right'caption='[[2dm6]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=IMN:INDOMETHACIN'>IMN</scene> and <scene name='pdbligand=TAM:TRIS(HYDROXYETHYL)AMINOMETHANE'>TAM</scene>
<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>
|ACTIVITY=  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
|GENE=  
<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.


'''Crystal structure of anti-configuration of indomethacin and leukotriene B4 12-hydroxydehydrogenase/15-oxo-prostaglandin 13-reductase complex'''
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>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2dm6" style="background-color:#fffaf0;"></div>


==Overview==
==See Also==
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.
*[[Leukotriene B4 hydroxydehydrogenase|Leukotriene B4 hydroxydehydrogenase]]
 
== References ==
==About this Structure==
<references/>
2DM6 is a [[Single protein]] structure of sequence from [http://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].
__TOC__
 
</StructureSection>
==Reference==
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:[http://www.ncbi.nlm.nih.gov/pubmed/16916844 16916844]
[[Category: Cavia porcellus]]
[[Category: Cavia porcellus]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Ago, H.]]
[[Category: Ago H]]
[[Category: Hori, T.]]
[[Category: Hori T]]
[[Category: Ishijima, J.]]
[[Category: Ishijima J]]
[[Category: Miyano, M.]]
[[Category: Miyano M]]
[[Category: RSGI, RIKEN Structural Genomics/Proteomics Initiative.]]
[[Category: Shimizu T]]
[[Category: Shimizu, T.]]
[[Category: Yokomizo T]]
[[Category: Yokomizo, T.]]
[[Category: IMN]]
[[Category: NAP]]
[[Category: TAM]]
[[Category: nad(p)-binding rossmann-fold domain]]
[[Category: riken structural genomics/proteomics initiative]]
[[Category: rsgi]]
[[Category: structural genomic]]
 
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Retrieved from "https://proteopedia.org/2dm6"