6UKD

Co-complex of S. pyogenes 10782 streptopain bound with a nitrile-based specific covalent inhibitor

6UKD の概要

• エントリーDOI: 10.2210/pdb6ukd/pdb
• 分子名称: Streptopain, benzyl [(2S)-1-(3-nitrophenyl)-3-oxobutan-2-yl]carbamate, NITRATE ION, ... (4 entities in total)
• 機能のキーワード: speb, streptopain, inhibitor, nitrile, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Streptococcus pyogenes ATCC 10782
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42018.30

構造登録者

Wolan, D.W.,Woehl, J.L.,Kitamura, S. (登録日: 2019-10-04, 公開日: 2020-09-09, 最終更新日: 2024-11-20)

主引用文献

Woehl, J.L.,Kitamura, S.,Dillon, N.,Han, Z.,Edgar, L.J.,Nizet, V.,Wolan, D.W.
An Irreversible Inhibitor to Probe the Role ofStreptococcus pyogenesCysteine Protease SpeB in Evasion of Host Complement Defenses.
Acs Chem.Biol., 15:2060-2069, 2020

PubMed Abstract: Members of the CA class of cysteine proteases have multifaceted roles in physiology and virulence for many bacteria. Streptococcal pyrogenic exotoxin B (SpeB) is secreted by and implicated in the pathogenesis of the bacterium through degradation of key human immune effector proteins. Here, we developed and characterized a clickable inhibitor, , based on X-ray crystallographic analysis and structure-activity relationships. Our SpeB probe showed irreversible enzyme inhibition in biochemical assays and labeled endogenous SpeB in cultured supernatants. Importantly, application of decreased survival in the presence of human neutrophils and supports the role of SpeB-mediated proteolysis as a mechanism to limit complement-mediated host defense. We posit that our SpeB inhibitor will be a useful chemical tool to regulate, label, and quantitate secreted cysteine proteases with SpeB-like activity in complex biological samples and a lead candidate for new therapeutics designed to sensitize to host immune clearance.

PubMed: 32662975
DOI: 10.1021/acschembio.0c00191

実験手法

X-RAY DIFFRACTION (1.589 Å)