5wdj

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CRYSTAL STRUCTURE OF MYELOPEROXIDASE SUBFORM C (MPO) COMPLEX WITH COMPOUND-6 AKA 7-(BENZYLOXY)-1H-[1,2, 3]TRIAZOLO[4,5-D]PYRIMIDIN-5-AMINE

Structural highlights

5wdj is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , , , ,
NonStd Res:
Gene:	MPO (HUMAN)
Activity:	Myeloperoxidase, with EC number 1.11.2.2
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.^[1] ^[2] ^[3] ^[4] ^[5]

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, a mammalian peroxidase involved in the immune system as an anti-microbial first responder, can produce hypochlorous acid in response to invading pathogens. Myeloperoxidase has been implicated in several chronic pathological diseases due to the chronic production of hypochlorous acid, as well as other reactive radical species. A high throughput screen and triaging protocol was developed to identify a reversible inhibitor of myeloperoxidase toward the potential treatment of chronic diseases such as atherosclerosis. The identification and characterization of a reversible myeloperoxidase inhibitor, 7-(benzyloxy)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine is described.

Triazolopyrimidines identified as reversible myeloperoxidase inhibitors.,Duclos F, Abell LM, Harden DG, Pike K, Nowak K, Locke GA, Duke GJ, Liu X, Fernando G, Shaw SA, Vokits BP, Wurtz NR, Viet A, Valente MN, Stachura S, Sleph P, Khan JA, Gao J, Dongre AR, Zhao L, Wexler RR, Gordon DA, Kick EK Medchemcomm. 2017 Oct 26;8(11):2093-2099. doi: 10.1039/c7md00268h. eCollection, 2017 Nov 1. PMID:30108726^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kizaki M, Miller CW, Selsted ME, Koeffler HP. Myeloperoxidase (MPO) gene mutation in hereditary MPO deficiency. Blood. 1994 Apr 1;83(7):1935-40. PMID:8142659
↑ Nauseef WM, Brigham S, Cogley M. Hereditary myeloperoxidase deficiency due to a missense mutation of arginine 569 to tryptophan. J Biol Chem. 1994 Jan 14;269(2):1212-6. PMID:7904599
↑ Nauseef WM, Cogley M, McCormick S. Effect of the R569W missense mutation on the biosynthesis of myeloperoxidase. J Biol Chem. 1996 Apr 19;271(16):9546-9. PMID:8621627
↑ DeLeo FR, Goedken M, McCormick SJ, Nauseef WM. A novel form of hereditary myeloperoxidase deficiency linked to endoplasmic reticulum/proteasome degradation. J Clin Invest. 1998 Jun 15;101(12):2900-9. PMID:9637725 doi:10.1172/JCI2649
↑ Romano M, Dri P, Dadalt L, Patriarca P, Baralle FE. Biochemical and molecular characterization of hereditary myeloperoxidase deficiency. Blood. 1997 Nov 15;90(10):4126-34. PMID:9354683
↑ Duclos F, Abell LM, Harden DG, Pike K, Nowak K, Locke GA, Duke GJ, Liu X, Fernando G, Shaw SA, Vokits BP, Wurtz NR, Viet A, Valente MN, Stachura S, Sleph P, Khan JA, Gao J, Dongre AR, Zhao L, Wexler RR, Gordon DA, Kick EK. Triazolopyrimidines identified as reversible myeloperoxidase inhibitors. Medchemcomm. 2017 Oct 26;8(11):2093-2099. doi: 10.1039/c7md00268h. eCollection, 2017 Nov 1. PMID:30108726 doi:http://dx.doi.org/10.1039/c7md00268h