6BMT

Crystal Structure of a Recombinant form of Human Myeloperoxidase Bound to an Inhibitor from Staphylococcus delphini

6BMT の概要

• エントリーDOI: 10.2210/pdb6bmt/pdb
• 関連するPDBエントリー: 5UZU
• 分子名称: Myeloperoxidase, Hypothetical Protein, CALCIUM ION, ... (7 entities in total)
• 機能のキーワード: myeloperoxidase, phagolysosome, staphylococcal inhibitor, innate immunity, oxidoreductase-inhibitor complex, oxidoreductase/inhibitor
• 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: 96709.79

構造登録者

Ploscariu, N.T.,Geisbrecht, B.V. (登録日: 2017-11-15, 公開日: 2018-01-03, 最終更新日: 2024-10-30)

主引用文献

Ploscariu, N.T.,de Jong, N.W.M.,van Kessel, K.P.M.,van Strijp, J.A.G.,Geisbrecht, B.V.
Identification and structural characterization of a novel myeloperoxidase inhibitor from Staphylococcus delphini.
Arch. Biochem. Biophys., 645:1-11, 2018

PubMed Abstract: Staphylococcus aureus and related species are highly adapted to their hosts and have evolved numerous strategies to evade the immune system. S. aureus shows resistance to killing following uptake into the phagosome, which suggests that the bacterium evades intracellular killing mechanisms used by neutrophils. We recently discovered an S. aureus protein (SPIN for Staphylococcal Peroxidase INhibitor) that binds to and inhibits myeloperoxidase (MPO), a major player in the oxidative defense of neutrophils. To allow for comparative studies between multiple SPIN sequences, we identified a panel of homologs from species closely related to S. aureus. Characterization of these proteins revealed that SPIN molecules from S. agnetis, S. delphini, S. schleiferi, and S. intermedius all bind human MPO with nanomolar affinities, and that those from S. delphini, S. schleiferi, and S. intermedius inhibit human MPO in a dose-dependent manner. A 2.4 Å resolution co-crystal structure of SPIN-delphini bound to recombinant human MPO allowed us to identify conserved structural features of SPIN proteins, and to propose sequence-dependent physical explanations for why SPIN-aureus binds human MPO with higher affinity than SPIN-delphini. Together, these studies expand our understanding of MPO binding and inhibition by a recently identified component of the staphylococcal innate immune evasion arsenal.

PubMed: 29524428
DOI: 10.1016/j.abb.2018.03.007

実験手法

X-RAY DIFFRACTION (2.403 Å)