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1kqu

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[[Image:1kqu.gif|left|200px]]<br />
 
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<applet load="1kqu" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1kqu, resolution 2.10&Aring;" />
 
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'''Human phospholipase A2 complexed with a substrate anologue'''<br />
 
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==Overview==
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==Human phospholipase A2 complexed with a substrate anologue==
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Few reported inhibitors of secretory phospholipase A(2) enzymes truly, inhibit the IIa human isoform (hnpsPLA(2)-IIa) noncovalently at, submicromolar concentrations. Herein, the simple chiral precursor, D-tyrosine was derivatised to give a series of potent new inhibitors of, hnpsPLA(2)-IIa. A 2.2-A crystal structure shows an inhibitor bound in the, active site of the enzyme, chelated to a Ca(2+) ion through carboxylate, and amide oxygen atoms, H-bonded through an amide NH group to His48, with, multiple hydrophobic contacts and a T-shaped aromatic-group-His6, interaction. Antiinflammatory activity is also demonstrated for two, compounds administered orally to rats.
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<StructureSection load='1kqu' size='340' side='right'caption='[[1kqu]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1kqu]] is a 1 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=1KQU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KQU 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]] 2.1&#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=BR4:6-PHENYL-4(R)-(7-PHENYL-HEPTANOYLAMINO)-HEXANOIC+ACID'>BR4</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=1kqu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kqu OCA], [https://pdbe.org/1kqu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1kqu RCSB], [https://www.ebi.ac.uk/pdbsum/1kqu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1kqu ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PA2GA_HUMAN PA2GA_HUMAN] Thought to participate in the regulation of the phospholipid metabolism in biomembranes including eicosanoid biosynthesis. Catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides.
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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/kq/1kqu_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1kqu 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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Few reported inhibitors of secretory phospholipase A(2) enzymes truly inhibit the IIa human isoform (hnpsPLA(2)-IIa) noncovalently at submicromolar concentrations. Herein, the simple chiral precursor D-tyrosine was derivatised to give a series of potent new inhibitors of hnpsPLA(2)-IIa. A 2.2-A crystal structure shows an inhibitor bound in the active site of the enzyme, chelated to a Ca(2+) ion through carboxylate and amide oxygen atoms, H-bonded through an amide NH group to His48, with multiple hydrophobic contacts and a T-shaped aromatic-group-His6 interaction. Antiinflammatory activity is also demonstrated for two compounds administered orally to rats.
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==Disease==
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D-Tyrosine as a chiral precusor to potent inhibitors of human nonpancreatic secretory phospholipase A2 (IIa) with antiinflammatory activity.,Hansford KA, Reid RC, Clark CI, Tyndall JD, Whitehouse MW, Guthrie T, McGeary RP, Schafer K, Martin JL, Fairlie DP Chembiochem. 2003 Mar 3;4(2-3):181-5. PMID:12616631<ref>PMID:12616631</ref>
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Known diseases associated with this structure: Colorectal cancer, sporadic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=172411 172411]]
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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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1KQU 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 CA and BR4 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phospholipase_A(2) Phospholipase A(2)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.4 3.1.1.4] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1KQU OCA].
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</div>
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<div class="pdbe-citations 1kqu" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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D-Tyrosine as a chiral precusor to potent inhibitors of human nonpancreatic secretory phospholipase A2 (IIa) with antiinflammatory activity., Hansford KA, Reid RC, Clark CI, Tyndall JD, Whitehouse MW, Guthrie T, McGeary RP, Schafer K, Martin JL, Fairlie DP, Chembiochem. 2003 Mar 3;4(2-3):181-5. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12616631 12616631]
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*[[Phospholipase A2 3D structures|Phospholipase A2 3D structures]]
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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: Phospholipase A(2)]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Martin JL]]
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[[Category: Martin, J.L.]]
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[[Category: Tyndall JD]]
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[[Category: Tyndall, J.D.]]
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[[Category: BR4]]
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[[Category: CA]]
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[[Category: inhibitor]]
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[[Category: phospholipase a2]]
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[[Category: structure]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:53:48 2007''
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Current revision

Human phospholipase A2 complexed with a substrate anologue

PDB ID 1kqu

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