2q7m: Difference between revisions

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[[Image:2q7m.jpg|left|200px]]


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==Crystal structure of human FLAP with MK-591==
The line below this paragraph, containing "STRUCTURE_2q7m", creates the "Structure Box" on the page.
<StructureSection load='2q7m' size='340' side='right'caption='[[2q7m]], [[Resolution|resolution]] 4.25&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<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>
or leave the SCENE parameter empty for the default display.
</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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<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>
{{STRUCTURE_2q7m|  PDB=2q7m  |  SCENE= }}
<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>
 
</table>
'''Crystal structure of human FLAP with MK-591'''
== Disease ==
 
[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.
 
== Function ==
==Overview==
[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>
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.
== Evolutionary Conservation ==
 
[[Image:Consurf_key_small.gif|200px|right]]
==About this Structure==
Check<jmol>
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].  
  <jmolCheckbox>
 
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/q7/2q7m_consurf.spt"</scriptWhenChecked>
==Reference==
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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]
    <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=2q7m ConSurf].
<div style="clear:both"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Ferguson, A D.]]
[[Category: Ferguson AD]]
[[Category: Flap]]
[[Category: Lipid transport]]
[[Category: Mapeg]]
[[Category: Membrane protein]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 14:29:24 2008''
Retrieved from "https://proteopedia.org/2q7m"