biostudies-literatureGrishkovskaya IBLRD VAAustrian Science Fund FWFNIAID NIH HHSNational Institutes of Health8244-8261https://www.ebi.ac.uk/biostudies/studies/S-EPMC5437232biostudies-literatureUnknown292(20)Myeloperoxidase (MPO) is synthesized by neutrophil and monocyte precursor cells and contributes to host defense by mediating microbial killing. Although several steps in MPO biosynthesis and processing have been elucidated, many questions remained, such as the structure-function relationship of monomeric unprocessed proMPO <i>versus</i> the mature dimeric MPO and the functional role of the propeptide. Here we have presented the first and high resolution (at 1.25 Å) crystal structure of proMPO and its solution structure obtained by small-angle X-ray scattering. Promyeloperoxidase hosts five occupied glycosylation sites and six intrachain cystine bridges with Cys-158 of the very flexible N-terminal propeptide being covalently linked to Cys-319 and thereby hindering homodimerization. FurthermThe Journal of biological chemistryStructure of human promyeloperoxidase (proMPO) and the role of the propeptide in processing and maturation.PMC5437232W 1224AI116546R01 AI116546I01 BX000513P01 AI044642AI044642Obinger CHofbauer SPaumann-Page MSoudi MGrishkovskaya IDjinovic-Carugo KTscheliessnig RStampler JNauseef WMFurtmuller PGSevcnikar BOostenbrink CfalseStructure of human promyeloperoxidase (proMPO) and the role of the propeptide in processing and maturation.Myeloperoxidase (MPO) is synthesized by neutrophil and monocyte precursor cells and contributes to host defense by mediating microbial killing. Although several steps in MPO biosynthesis and processing have been elucidated, many questions remained, such as the structure-function relationship of monomeric unprocessed proMPO <i>versus</i> the mature dimeric MPO and the functional role of the propeptide. Here we have presented the first and high resolution (at 1.25 Å) crystal structure of proMPO and its solution structure obtained by small-angle X-ray scattering. Promyeloperoxidase hosts five occupied glycosylation sites and six intrachain cystine bridges with Cys-158 of the very flexible N-terminal propeptide being covalently linked to Cys-319 and thereby hindering homodimerization. Furtherm2017-01-01T00:00:00Z2017 May2025-04-26T06:03:49.854Z2019-03-27T02:45:23ZS-EPMC54372322834807910.1074/jbc.M117.775031