6g5j

Secreted phospholipase A2 type X in complex with ligand

spinqualitylabelsall models 6g5j, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6g5j is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.85Å Ligands: CA, DMS, EM8, PEG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PA2GX_HUMAN PA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides. Has a powerful potency for releasing arachidonic acid from cell membrane phospholipids. Prefers phosphatidylethanolamine and phosphatidylcholine liposomes to those of phosphatidylserine. Publication Abstract from PubMed A lead generation campaign identified indole-based sPLA2-X inhibitors with a promising selectivity profile against other sPLA2 isoforms. Further optimization of sPLA2 selectivity and metabolic stability resulted in the design of (-)-17, a novel, potent, and selective sPLA2-X inhibitor with an exquisite pharmacokinetic profile characterized by high absorption and low clearance, and low toxicological risk. Compound (-)-17 was tested in an ApoE(-/-) murine model of atherosclerosis to evaluate the effect of reversible, pharmacological sPLA2-X inhibition on atherosclerosis development. Despite being well tolerated and achieving adequate systemic exposure of mechanistic relevance, (-)-17 did not significantly affect circulating lipid and lipoprotein biomarkers and had no effect on coronary function or histological markers of atherosclerosis. Design of Selective sPLA2-X Inhibitor (-)-2-{2-[Carbamoyl-6-(trifluoromethoxy)-1H-indol-1-yl]pyridine-2-yl}propanoic Acid.,Giordanetto F, Knerr L, Nordberg P, Pettersen D, Selmi N, Beisel HG, de la Motte H, Mansson A, Dahlstrom M, Broddefalk J, Saarinen G, Klingegard F, Hurt-Camejo E, Rosengren B, Wikstrom J, Wagberg M, Brengdahl J, Rohman M, Sandmark J, Akerud T, Roth RG, Jansen F, Ahlqvist M ACS Med Chem Lett. 2018 Jun 23;9(7):600-605. doi: 10.1021/acsmedchemlett.7b00507., eCollection 2018 Jul 12. PMID:30034586 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Phospholipase A2 3D structures

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