5qj2

CRYSTAL STRUCTURE OF MYELOPEROXIDASE SUBFORM C (MPO) OMPLEX WITH COMPOUND-20 AKA 7-((3-(1-METHYL-1H-PYRAZOL-3- YL)BENZYL)OXY)- 1H-[1,2,3]TRIAZOLO[4,5-B]PYRIDIN-5-AMINE

spinqualitylabelsall models 5qj2, resolution 2.82Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5qj2 is a 8 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 2.82Å Ligands: BMA, CA, CL, FUC, HEM, JXS, MAN, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease PERM_HUMAN Defects in MPO are the cause of myeloperoxidase deficiency (MPOD) [MIM:254600. A disorder characterized by decreased myeloperoxidase activity in neutrophils and monocytes that results in disseminated candidiasis. Function PERM_HUMAN Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of hypohalous acids, primarily hypochlorous acid in physiologic situations, and other toxic intermediates that greatly enhance PMN microbicidal activity. Publication Abstract from PubMed Myeloperoxidase (MPO) generates reactive oxygen species that potentially contribute to many chronic inflammatory diseases. A recently reported triazolopyrimidine MPO inhibitor was optimized to improve acid stability and remove methyl guanine methyl transferase (MGMT) activity. Multiple synthetic routes were explored that allowed rapid optimization of a key benzyl ether side chain. Crystal structures of inhibitors bound to the MPO active site demonstrated alternate binding modes and guided rational design of MPO inhibitors. Thioether 36 showed significant inhibition of MPO activity in an acute mouse inflammation model after oral dosing. Potent Triazolopyridine Myeloperoxidase Inhibitors.,Wurtz NR, Viet A, Shaw SA, Dilger A, Valente MN, Khan JA, Jusuf S, Narayanan R, Fernando G, Lo F, Liu X, Locke GA, Kopcho L, Abell LM, Sleph P, Basso M, Zhao L, Wexler RR, Duclos F, Kick EK ACS Med Chem Lett. 2018 Nov 1;9(12):1175-1180. doi: , 10.1021/acsmedchemlett.8b00308. eCollection 2018 Dec 13. PMID:30613322 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Myeloperoxidase

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