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1v3v

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(New page: 200px<br /><applet load="1v3v" size="450" color="white" frame="true" align="right" spinBox="true" caption="1v3v, resolution 2.0&Aring;" /> '''Crystal structure of ...)
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[[Image:1v3v.gif|left|200px]]<br /><applet load="1v3v" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1v3v, resolution 2.0&Aring;" />
 
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'''Crystal structure of leukotriene B4 12-hydroxydehydrogenase/15-oxo-prostaglandin 13-reductase complexed with NADP and 15-oxo-PGE2'''<br />
 
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==Overview==
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==Crystal structure of leukotriene B4 12-hydroxydehydrogenase/15-oxo-prostaglandin 13-reductase complexed with NADP and 15-oxo-PGE2==
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The bifunctional leukotriene B(4), 12-hydroxydehydrogenase/15-oxo-prostaglandin 13-reductase (LTB(4), 12-HD/PGR) is an essential enzyme for eicosanoid inactivation. It is, involved in the metabolism of the E and F series of 15-oxo-prostaglandins, (15-oxo-PGs), leukotriene B(4) (LTB(4)), and 15-oxo-lipoxin A(4), (15-oxo-LXA(4)). Some nonsteroidal anti-inflammatory drugs (NSAIDs), which, primarily act as cyclooxygenase inhibitors also inhibit LTB(4) 12-HD/PGR, activity. Here we report the crystal structure of the LTB(4) 12-HD/PGR, the binary complex structure with NADP(+), and the ternary complex, structure with NADP(+) and 15-oxo-PGE(2). In the ternary complex, both in, the crystalline form and in solution, the enolate anion intermediate, accumulates as a brown chromophore. PGE(2) contains two chains, but only, the omega-chain of 15-oxo-PGE(2) was defined in the electron density map, in the ternary complex structure. The omega-chain was identified at the, hydrophobic pore on the dimer interface. The structure showed that the, 15-oxo group forms hydrogen bonds with the 2'-hydroxyl group of nicotine, amide ribose of NADP(+) and a bound water molecule to stabilize the, enolate intermediate during the reductase reaction. The electron-deficient, C13 atom of the conjugated enolate may be directly attacked by a hydride, from the NADPH nicotine amide in a stereospecific manner. The moderate, recognition of 15-oxo-PGE(2) is consistent with a broad substrate, specificity of LTB(4) 12-HD/PGR. The structure also implies that a Src, homology domain 3 may interact with the left-handed proline-rich helix at, the dimer interface and regulate LTB(4) 12-HD/PGR activity by disruption, of the substrate binding pore to accommodate the omega-chain.
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<StructureSection load='1v3v' size='340' side='right'caption='[[1v3v]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1v3v]] 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=1V3V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1V3V FirstGlance]. <br>
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</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>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5OP:(5E,13E)-11-HYDROXY-9,15-DIOXOPROSTA-5,13-DIEN-1-OIC+ACID'>5OP</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1v3v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1v3v OCA], [https://pdbe.org/1v3v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1v3v RCSB], [https://www.ebi.ac.uk/pdbsum/1v3v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1v3v ProSAT], [https://www.topsan.org/Proteins/RSGI/1v3v TOPSAN]</span></td></tr>
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</table>
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== Function ==
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[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.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/v3/1v3v_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1v3v ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The bifunctional leukotriene B(4) 12-hydroxydehydrogenase/15-oxo-prostaglandin 13-reductase (LTB(4) 12-HD/PGR) is an essential enzyme for eicosanoid inactivation. It is involved in the metabolism of the E and F series of 15-oxo-prostaglandins (15-oxo-PGs), leukotriene B(4) (LTB(4)), and 15-oxo-lipoxin A(4) (15-oxo-LXA(4)). Some nonsteroidal anti-inflammatory drugs (NSAIDs), which primarily act as cyclooxygenase inhibitors also inhibit LTB(4) 12-HD/PGR activity. Here we report the crystal structure of the LTB(4) 12-HD/PGR, the binary complex structure with NADP(+), and the ternary complex structure with NADP(+) and 15-oxo-PGE(2). In the ternary complex, both in the crystalline form and in solution, the enolate anion intermediate accumulates as a brown chromophore. PGE(2) contains two chains, but only the omega-chain of 15-oxo-PGE(2) was defined in the electron density map in the ternary complex structure. The omega-chain was identified at the hydrophobic pore on the dimer interface. The structure showed that the 15-oxo group forms hydrogen bonds with the 2'-hydroxyl group of nicotine amide ribose of NADP(+) and a bound water molecule to stabilize the enolate intermediate during the reductase reaction. The electron-deficient C13 atom of the conjugated enolate may be directly attacked by a hydride from the NADPH nicotine amide in a stereospecific manner. The moderate recognition of 15-oxo-PGE(2) is consistent with a broad substrate specificity of LTB(4) 12-HD/PGR. The structure also implies that a Src homology domain 3 may interact with the left-handed proline-rich helix at the dimer interface and regulate LTB(4) 12-HD/PGR activity by disruption of the substrate binding pore to accommodate the omega-chain.
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==About this Structure==
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Structural basis of leukotriene B4 12-hydroxydehydrogenase/15-Oxo-prostaglandin 13-reductase catalytic mechanism and a possible Src homology 3 domain binding loop.,Hori T, Yokomizo T, Ago H, Sugahara M, Ueno G, Yamamoto M, Kumasaka T, Shimizu T, Miyano M J Biol Chem. 2004 May 21;279(21):22615-23. Epub 2004 Mar 8. PMID:15007077<ref>PMID:15007077</ref>
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1V3V is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Cavia_porcellus Cavia porcellus] with CL, NAP and 5OP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/15-oxoprostaglandin_13-oxidase 15-oxoprostaglandin 13-oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.48 1.3.1.48] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1V3V OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Structural basis of leukotriene B4 12-hydroxydehydrogenase/15-Oxo-prostaglandin 13-reductase catalytic mechanism and a possible Src homology 3 domain binding loop., Hori T, Yokomizo T, Ago H, Sugahara M, Ueno G, Yamamoto M, Kumasaka T, Shimizu T, Miyano M, J Biol Chem. 2004 May 21;279(21):22615-23. Epub 2004 Mar 8. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15007077 15007077]
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</div>
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[[Category: 15-oxoprostaglandin 13-oxidase]]
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<div class="pdbe-citations 1v3v" style="background-color:#fffaf0;"></div>
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[[Category: Cavia porcellus]]
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[[Category: Single protein]]
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[[Category: Ago, H.]]
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[[Category: Hori, T.]]
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[[Category: Kumasaka, T.]]
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[[Category: Miyano, M.]]
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[[Category: RSGI, RIKEN.Structural.Genomics/Proteomics.Initiative.]]
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[[Category: Shimizu, T.]]
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[[Category: Sugahara, M.]]
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[[Category: Ueno, G.]]
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[[Category: Yamamoto, M.]]
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[[Category: Yokomizo, T.]]
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[[Category: 5OP]]
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[[Category: CL]]
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[[Category: NAP]]
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[[Category: riken structural genomics/proteomics initiative]]
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[[Category: rossmann fold]]
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[[Category: rsgi]]
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[[Category: structural genomics]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 04:25:32 2007''
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==See Also==
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*[[Leukotriene B4 hydroxydehydrogenase|Leukotriene B4 hydroxydehydrogenase]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Cavia porcellus]]
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[[Category: Large Structures]]
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[[Category: Ago H]]
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[[Category: Hori T]]
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[[Category: Kumasaka T]]
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[[Category: Miyano M]]
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[[Category: Shimizu T]]
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[[Category: Sugahara M]]
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[[Category: Ueno G]]
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[[Category: Yamamoto M]]
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[[Category: Yokomizo T]]

Current revision

Crystal structure of leukotriene B4 12-hydroxydehydrogenase/15-oxo-prostaglandin 13-reductase complexed with NADP and 15-oxo-PGE2

PDB ID 1v3v

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