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| | ==Functionally selective inhibition of Group IIA phospholipase A2 reveals a role for vimentin in regulating arachidonic acid metabolism== | | ==Functionally selective inhibition of Group IIA phospholipase A2 reveals a role for vimentin in regulating arachidonic acid metabolism== |
| - | <StructureSection load='3u8i' size='340' side='right' caption='[[3u8i]], [[Resolution|resolution]] 1.10Å' scene=''> | + | <StructureSection load='3u8i' size='340' side='right'caption='[[3u8i]], [[Resolution|resolution]] 1.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3u8i]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3U8I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3U8I FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3u8i]] is a 2 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=3U8I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3U8I FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.1Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=OLD:3-[2-(4-BROMOPHENYL)-2-OXOETHYL]-L-HISTIDINE'>OLD</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=OLD:3-[2-(4-BROMOPHENYL)-2-OXOETHYL]-L-HISTIDINE'>OLD</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3u8b|3u8b]], [[3u8d|3u8d]], [[3u8h|3u8h]]</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3u8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u8i OCA], [https://pdbe.org/3u8i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3u8i RCSB], [https://www.ebi.ac.uk/pdbsum/3u8i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3u8i ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PLA2G2A, PLA2B, PLA2L, RASF-A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3u8i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u8i OCA], [http://pdbe.org/3u8i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3u8i RCSB], [http://www.ebi.ac.uk/pdbsum/3u8i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3u8i ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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. | + | [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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Phospholipase A2|Phospholipase A2]] | + | *[[Phospholipase A2 3D structures|Phospholipase A2 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Bouveret, R]] | + | [[Category: Large Structures]] |
| - | [[Category: Bryant, K J]] | + | [[Category: Bouveret R]] |
| - | [[Category: Church, W B]] | + | [[Category: Bryant KJ]] |
| - | [[Category: Cunningham, A M]] | + | [[Category: Church WB]] |
| - | [[Category: Curmi, P M]] | + | [[Category: Cunningham AM]] |
| - | [[Category: Duff, A P]] | + | [[Category: Curmi PM]] |
| - | [[Category: Gelb, M H]] | + | [[Category: Duff AP]] |
| - | [[Category: Gray, P P]] | + | [[Category: Gelb MH]] |
| - | [[Category: Harrop, S J]] | + | [[Category: Gray PP]] |
| - | [[Category: Harvey, R P]] | + | [[Category: Harrop SJ]] |
| - | [[Category: Huang, E P]] | + | [[Category: Harvey RP]] |
| - | [[Category: Lee, L K]] | + | [[Category: Huang EP]] |
| - | [[Category: Lei, P W]] | + | [[Category: Lee LK]] |
| - | [[Category: Scott, K F]] | + | [[Category: Lei P-W]] |
| - | [[Category: Hydrolase]]
| + | [[Category: Scott KF]] |
| - | [[Category: Secreted phospholipase a2]]
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| Structural highlights
Function
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.
Publication Abstract from PubMed
Human group IIA secreted phospholipase A2 (hGIIA) promotes tumor growth and inflammation and can act independently of its well described catalytic lipase activity via an alternative poorly understood signaling pathway. With six chemically diverse inhibitors we show that it is possible to selectively inhibit hGIIA signaling over catalysis, and x-ray crystal structures illustrate that signaling involves a pharmacologically distinct surface to the catalytic site. We demonstrate in rheumatoid fibroblast-like synoviocytes that non-catalytic signaling is associated with rapid internalization of the enzyme and colocalization with vimentin. Trafficking of exogenous hGIIA was monitored with immunofluorescence studies, which revealed that vimentin localization is disrupted by inhibitors of signaling that belong to a rare class of small molecule inhibitors that modulate protein-protein interactions. This study provides structural and pharmacological evidence for an association between vimentin, hGIIA, and arachidonic acid metabolism in synovial inflammation, avenues for selective interrogation of hGIIA signaling, and new strategies for therapeutic hGIIA inhibitor design.
Selective Inhibition of Human Group IIA-secreted Phospholipase A2 (hGIIA) Signaling Reveals Arachidonic Acid Metabolism Is Associated with Colocalization of hGIIA to Vimentin in Rheumatoid Synoviocytes.,Lee LK, Bryant KJ, Bouveret R, Lei PW, Duff AP, Harrop SJ, Huang EP, Harvey RP, Gelb MH, Gray PP, Curmi PM, Cunningham AM, Church WB, Scott KF J Biol Chem. 2013 May 24;288(21):15269-79. doi: 10.1074/jbc.M112.397893. Epub, 2013 Mar 12. PMID:23482564[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lee LK, Bryant KJ, Bouveret R, Lei PW, Duff AP, Harrop SJ, Huang EP, Harvey RP, Gelb MH, Gray PP, Curmi PM, Cunningham AM, Church WB, Scott KF. Selective Inhibition of Human Group IIA-secreted Phospholipase A2 (hGIIA) Signaling Reveals Arachidonic Acid Metabolism Is Associated with Colocalization of hGIIA to Vimentin in Rheumatoid Synoviocytes. J Biol Chem. 2013 May 24;288(21):15269-79. doi: 10.1074/jbc.M112.397893. Epub, 2013 Mar 12. PMID:23482564 doi:10.1074/jbc.M112.397893
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