UGSF, CNRS, 50 Avenue de Halley, 59658 Villeneuve d'Ascq, France.
Department of Pharmacognosy, Bioanalysis and Drug Discovery, Faculty of Pharmacy, Université Libre De Bruxelles, Brussels, Belgium.
Acta Crystallogr D Struct Biol. 2022 Sep 1;78(Pt 9):1099-1109. doi: 10.1107/S2059798322007082. Epub 2022 Aug 9.
Human myeloperoxidase (MPO) utilizes hydrogen peroxide to oxidize organic compounds and as such plays an essential role in cell-component synthesis, in metabolic and elimination pathways, and in the front-line defence against pathogens. Moreover, MPO is increasingly being reported to play a role in inflammation. The enzymatic activity of MPO has also been shown to depend on its glycosylation. Mammalian MPO crystal structures deposited in the Protein Data Bank (PDB) present only a partial identification of their glycosylation. Here, a newly obtained crystal structure of MPO containing four disulfide-linked dimers and showing an elaborate collection of glycans is reported. These are compared with the glycans identified in proteomics studies and from 18 human MPO structures available in the PDB. The crystal structure also contains bound paroxetine, a blocker of serotonin reuptake that has previously been identified as an irreversible inhibitor of MPO, in the presence of thiocyanate, a physiological substrate of MPO.
人髓过氧化物酶（MPO）利用过氧化氢氧化有机化合物，因此在细胞成分合成、代谢和消除途径以及抵御病原体的一线防御中发挥着重要作用。此外，MPO 被越来越多地报道在炎症中发挥作用。MPO 的酶活性也被证明依赖于其糖基化。储存在蛋白质数据库（PDB）中的哺乳动物 MPO 晶体结构仅部分鉴定了其糖基化。在这里，报道了一种新获得的 MPO 晶体结构，其中包含四个二硫键连接的二聚体，并显示出精心收集的聚糖。这些与蛋白质组学研究中鉴定的聚糖以及 PDB 中可用的 18 个人类 MPO 结构中的聚糖进行了比较。晶体结构还包含帕罗西汀，一种 5-羟色胺再摄取抑制剂，它以前被鉴定为 MPO 的不可逆抑制剂，在硫氰酸盐存在下，这是 MPO 的一种生理底物。
