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2q7r

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(New page: 200px<br /> <applet load="2q7r" size="450" color="white" frame="true" align="right" spinBox="true" caption="2q7r, resolution 4.00&Aring;" /> '''Crystal structure o...)
Current revision (08:11, 25 June 2021) (edit) (undo)
 
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[[Image:2q7r.gif|left|200px]]<br />
 
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<applet load="2q7r" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2q7r, resolution 4.00&Aring;" />
 
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'''Crystal structure of human FLAP with an iodinated analog of MK-591'''<br />
 
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==Overview==
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==Crystal structure of human FLAP with an iodinated analog of MK-591==
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Leukotrienes are proinflammatory products of arachidonic acid oxidation by, 5-lipoxygenase that have been shown to be involved in respiratory and, cardiovascular diseases. The integral membrane protein FLAP is essential, for leukotriene biosynthesis. We describe the x-ray crystal structures of, human FLAP in complex with two leukotriene biosynthesis inhibitors at 4.0, and 4.2 angstrom resolution, respectively. The structures show that, inhibitors bind in membrane-embedded pockets of FLAP, which suggests how, these inhibitors prevent arachidonic acid from binding to FLAP and, subsequently being transferred to 5-lipoxygenase, thereby preventing, leukotriene biosynthesis. This structural information provides a platform, for the development of therapeutics for respiratory and cardiovascular, diseases.
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<StructureSection load='2q7r' size='340' side='right'caption='[[2q7r]], [[Resolution|resolution]] 4.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2q7r]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q7R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q7R FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3CS:3-[3-(3,3-DIMETHYLBUTANOYL)-1-(4-IODOBENZYL)-5-(QUINOLIN-2-YLMETHOXY)-1H-INDOL-2-YL]-2,2-DIMETHYLPROPANOIC+ACID'>3CS</scene></td></tr>
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2q7m|2q7m]]</div></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ALOX5AP, FLAP ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2q7r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q7r OCA], [https://pdbe.org/2q7r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q7r RCSB], [https://www.ebi.ac.uk/pdbsum/2q7r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q7r ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[[https://www.uniprot.org/uniprot/AL5AP_HUMAN AL5AP_HUMAN]] Genetic variations in ALOX5AP may be a cause of susceptibility to ischemic stroke (ISCHSTR) [MIM:[https://omim.org/entry/601367 601367]]; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.<ref>PMID:14770184</ref> Note=Genetic variations in ALOX5AP may be associated with susceptibility to myocardial infarction. Involvement in myocardial infarction is however unclear: according to some authors (PubMed:14770184), a 4-SNP haplotype in ALOX5AP confers risk of myocardial infarction, while according to other (PubMed:17304054) ALOX5AP is not implicated in this condition.
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== Function ==
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[[https://www.uniprot.org/uniprot/AL5AP_HUMAN AL5AP_HUMAN]] Required for leukotriene biosynthesis by ALOX5 (5-lipoxygenase). Anchors ALOX5 to the membrane. Binds arachidonic acid, and could play an essential role in the transfer of arachidonic acid to ALOX5. Binds to MK-886, a compound that blocks the biosynthesis of leukotrienes.<ref>PMID:2300173</ref> <ref>PMID:8440384</ref>
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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/q7/2q7r_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=2q7r 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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Leukotrienes are proinflammatory products of arachidonic acid oxidation by 5-lipoxygenase that have been shown to be involved in respiratory and cardiovascular diseases. The integral membrane protein FLAP is essential for leukotriene biosynthesis. We describe the x-ray crystal structures of human FLAP in complex with two leukotriene biosynthesis inhibitors at 4.0 and 4.2 angstrom resolution, respectively. The structures show that inhibitors bind in membrane-embedded pockets of FLAP, which suggests how these inhibitors prevent arachidonic acid from binding to FLAP and subsequently being transferred to 5-lipoxygenase, thereby preventing leukotriene biosynthesis. This structural information provides a platform for the development of therapeutics for respiratory and cardiovascular diseases.
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==Disease==
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Crystal structure of inhibitor-bound human 5-lipoxygenase-activating protein.,Ferguson AD, McKeever BM, Xu S, Wisniewski D, Miller DK, Yamin TT, Spencer RH, Chu L, Ujjainwalla F, Cunningham BR, Evans JF, Becker JW Science. 2007 Jul 27;317(5837):510-2. Epub 2007 Jun 28. PMID:17600184<ref>PMID:17600184</ref>
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Known diseases associated with this structure: Myocardial infarction, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603700 603700]], Stroke, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603700 603700]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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2Q7R 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 3CS as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2Q7R OCA].
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</div>
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<div class="pdbe-citations 2q7r" style="background-color:#fffaf0;"></div>
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==Reference==
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== References ==
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Crystal structure of inhibitor-bound human 5-lipoxygenase-activating protein., Ferguson AD, McKeever BM, Xu S, Wisniewski D, Miller DK, Yamin TT, Spencer RH, Chu L, Ujjainwalla F, Cunningham BR, Evans JF, Becker JW, Science. 2007 Jul 27;317(5837):510-2. Epub 2007 Jun 28. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17600184 17600184]
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<references/>
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[[Category: Homo sapiens]]
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__TOC__
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[[Category: Single protein]]
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</StructureSection>
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[[Category: Ferguson, A.D.]]
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[[Category: Human]]
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[[Category: 3CS]]
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[[Category: Large Structures]]
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[[Category: flap]]
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[[Category: Ferguson, A D]]
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[[Category: lipid transport]]
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[[Category: Flap]]
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[[Category: mapeg]]
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[[Category: Lipid transport]]
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[[Category: membrane protein]]
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[[Category: Mapeg]]
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[[Category: Membrane protein]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 23:30:47 2007''
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Current revision

Crystal structure of human FLAP with an iodinated analog of MK-591

PDB ID 2q7r

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