5i9i
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | The entry | + | ==Crystal structure of LP_PLA2 in complex with Darapladib== |
| + | <StructureSection load='5i9i' size='340' side='right' caption='[[5i9i]], [[Resolution|resolution]] 2.70Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5i9i]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I9I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5I9I FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5HV:N-[2-(DIETHYLAMINO)ETHYL]-2-{2-[(4-FLUOROBENZYL)SULFANYL]-4-OXO-4,5,6,7-TETRAHYDRO-1H-CYCLOPENTA[D]PYRIMIDIN-1-YL}-N-{[4-(TRIFLUOROMETHYL)BIPHENYL-4-YL]METHYL}ACETAMIDE'>5HV</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5i8p|5i8p]]</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/1-alkyl-2-acetylglycerophosphocholine_esterase 1-alkyl-2-acetylglycerophosphocholine esterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.47 3.1.1.47] </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=5i9i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i9i OCA], [http://pdbe.org/5i9i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i9i RCSB], [http://www.ebi.ac.uk/pdbsum/5i9i PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/PAFA_HUMAN PAFA_HUMAN]] Defects in PLA2G7 are the cause of platelet-activating factor acetylhydrolase deficiency (PAFAD) [MIM:[http://omim.org/entry/614278 614278]]. An enzymatic deficiency that results in exacerbated bodily response to inflammatory agents. Asthmatic individuals affected by this condition may manifest severe respiratory symptoms.<ref>PMID:8675689</ref> <ref>PMID:9245731</ref> <ref>PMID:9412624</ref> <ref>PMID:9472966</ref> <ref>PMID:9759612</ref> Defects in PLA2G7 are a cause of susceptibility to asthma (ASTHMA) [MIM:[http://omim.org/entry/600807 600807]]. The most common chronic disease affecting children and young adults. It is a complex genetic disorder with a heterogeneous phenotype, largely attributed to the interactions among many genes and between these genes and the environment. It is characterized by recurrent attacks of paroxysmal dyspnea, with weezing due to spasmodic contraction of the bronchi. Note=PLA2G7 variants can be a risk factor for the development of asthma and PLA2G7 may act as a modifier gene that modulates the severity of this disease.<ref>PMID:10733466</ref> Defects in PLA2G7 are a cause of susceptibility to atopic hypersensitivity (ATOPY) [MIM:[http://omim.org/entry/147050 147050]]. A condition characterized by predisposition to develop hypersensitivity reactions. Atopic individuals can develop eczema, allergic rhinitis and allergic asthma.<ref>PMID:10733466</ref> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/PAFA_HUMAN PAFA_HUMAN]] Modulates the action of platelet-activating factor (PAF) by hydrolyzing the sn-2 ester bond to yield the biologically inactive lyso-PAF. Has a specificity for substrates with a short residue at the sn-2 position. It is inactive against long-chain phospholipids. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Lipoprotein-associated phospholipase A2 (Lp-PLA2) represents a promising therapeutic target for atherosclerosis and Alzheimer's disease. Here we reported the first crystal structures of Lp-PLA2 bound with reversible inhibitors and the thermodynamic characterization of complexes. High rigidity of Lp-PLA2 structure and similar binding modes of inhibitors with completely different scaffolds are revealed. It not only provides the molecular basis for inhibitory activity but also sheds light on the essential features of Lp-PLA2 recognition with reversible inhibitors. | ||
| - | + | Structural and Thermodynamic Characterization of Protein-Ligand Interactions Formed between Lipoprotein-Associated Phospholipase A2 and Inhibitors.,Liu Q, Chen X, Chen W, Yuan X, Su H, Shen J, Xu Y J Med Chem. 2016 May 26;59(10):5115-20. doi: 10.1021/acs.jmedchem.6b00282. Epub, 2016 Apr 26. PMID:27078579<ref>PMID:27078579</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Xu, Y | + | <div class="pdbe-citations 5i9i" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: 1-alkyl-2-acetylglycerophosphocholine esterase]] | ||
| + | [[Category: Liu, Q F]] | ||
| + | [[Category: Xu, Y C]] | ||
| + | [[Category: Hydrolase-hydrolase inhibitor complex]] | ||
| + | [[Category: Lp_pla2 inhibitor]] | ||
Revision as of 15:14, 20 June 2016
Crystal structure of LP_PLA2 in complex with Darapladib
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