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2q7m

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[[Image:2q7m.jpg|left|200px]]
 
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{{Structure
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==Crystal structure of human FLAP with MK-591==
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|PDB= 2q7m |SIZE=350|CAPTION= <scene name='initialview01'>2q7m</scene>, resolution 4.25&Aring;
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<StructureSection load='2q7m' size='340' side='right'caption='[[2q7m]], [[Resolution|resolution]] 4.25&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=2CS:3-[3-(TERT-BUTYLTHIO)-1-(4-CHLOROBENZYL)-5-(QUINOLIN-2-YLMETHOXY)-1H-INDOL-2-YL]-2,2-DIMETHYLPROPANOIC ACID'>2CS</scene>
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<table><tr><td colspan='2'>[[2q7m]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q7M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q7M FirstGlance]. <br>
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|ACTIVITY=
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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]] 4.25&#8491;</td></tr>
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|GENE= ALOX5AP, FLAP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2CS:3-[3-(TERT-BUTYLTHIO)-1-(4-CHLOROBENZYL)-5-(QUINOLIN-2-YLMETHOXY)-1H-INDOL-2-YL]-2,2-DIMETHYLPROPANOIC+ACID'>2CS</scene></td></tr>
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}}
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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=2q7m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q7m OCA], [https://pdbe.org/2q7m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q7m RCSB], [https://www.ebi.ac.uk/pdbsum/2q7m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q7m ProSAT]</span></td></tr>
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</table>
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'''Crystal structure of human FLAP with MK-591'''
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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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==Overview==
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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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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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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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==Disease==
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Check<jmol>
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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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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/q7/2q7m_consurf.spt"</scriptWhenChecked>
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==About this Structure==
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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2Q7M is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q7M OCA].
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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==Reference==
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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=2q7m ConSurf].
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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://www.ncbi.nlm.nih.gov/pubmed/17600184 17600184]
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<div style="clear:both"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Ferguson, A D.]]
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[[Category: Ferguson AD]]
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[[Category: 2CS]]
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[[Category: flap]]
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[[Category: lipid transport]]
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[[Category: mapeg]]
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[[Category: membrane protein]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:22:43 2008''
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Current revision

Crystal structure of human FLAP with MK-591

PDB ID 2q7m

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