8OGI

Structure of native human eosinophil peroxidase

8OGI の概要

• エントリーDOI: 10.2210/pdb8ogi/pdb
• 分子名称: Eosinophil peroxidase light chain, ACETATE ION, CALCIUM ION, ... (12 entities in total)
• 機能のキーワード: hydrogen peroxide-dependent heme peroxidase immune system eosinophiles, oxidoreductase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 68450.89

構造登録者

Pfanzagl, V.,Obinger, C. (登録日: 2023-03-20, 公開日: 2024-01-24, 最終更新日: 2024-10-23)

主引用文献

Pfanzagl, V.,Gruber-Grunwald, C.,Leitgeb, U.,Furtmuller, P.G.,Obinger, C.
Posttranslational modification and heme cavity architecture of human eosinophil peroxidase-insights from first crystal structure and biochemical characterization.
J.Biol.Chem., 299:105402-105402, 2023

PubMed Abstract: Eosinophil peroxidase (EPO) is the most abundant granule protein exocytosed by eosinophils, specialized human phagocytes. Released EPO catalyzes the formation of reactive oxidants from bromide, thiocyanate, and nitrite that kill tissue-invading parasites. However, EPO also plays a deleterious role in inflammatory diseases, making it a potential pharmacological target. A major hurdle is the high similarity to the homologous myeloperoxidase (MPO), which requires a detailed understanding of the small structural differences that can be used to increase the specificity of the inhibitors. Here, we present the first crystal structure of mature leukocyte EPO at 1.6 Å resolution together with analyses of its posttranslational modifications and biochemical properties. EPO has an exceptionally high number of positively charged surface patches but only two occupied glycosylation sites. The crystal structure further revealed the existence of a light (L) and heavy (H) chain as a result of proteolytic cleavage. Detailed comparison with the structure of human MPO allows us to identify differences that may contribute to the known divergent enzymatic properties. The crystal structure revealed fully established ester links between the prosthetic group and the protein, the comparably weak imidazolate character of the proximal histidine, and the conserved structure of the catalytic amino acids and Ca-binding site. Prediction of the structure of unprocessed proeosinophil peroxidase allows further structural analysis of the three protease cleavage sites and the potential pro-convertase recognition site in the propeptide. Finally, EPO biosynthesis and its biochemical and biophysical properties are discussed with respect to the available data from the well-studied MPO.

PubMed: 38229400
DOI: 10.1016/j.jbc.2023.105402

実験手法

X-RAY DIFFRACTION (1.547 Å)