7MCN

Crystal structure of Staphylococcus aureus Cystathionine gamma-lyase, Holoenzyme with High HEPES

7MCN の概要

• エントリーDOI: 10.2210/pdb7mcn/pdb
• 分子名称: Bifunctional cystathionine gamma-lyase/homocysteine desulfhydrase, PYRIDOXAL-5'-PHOSPHATE, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, ... (6 entities in total)
• 機能のキーワード: amino-acid biosynthesis, cysteine biosynthesis, hydrogen sulfide production, plp dependent enzyme, lyase
• 由来する生物種: Staphylococcus aureus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42409.51

構造登録者

Nuthanakanti, A.,Serganov, A.,Kaushik, A. (登録日: 2021-04-02, 公開日: 2021-06-23, 最終更新日: 2023-11-15)

主引用文献

Shatalin, K.,Nuthanakanti, A.,Kaushik, A.,Shishov, D.,Peselis, A.,Shamovsky, I.,Pani, B.,Lechpammer, M.,Vasilyev, N.,Shatalina, E.,Rebatchouk, D.,Mironov, A.,Fedichev, P.,Serganov, A.,Nudler, E.
Inhibitors of bacterial H 2 S biogenesis targeting antibiotic resistance and tolerance.
Science, 372:1169-1175, 2021

PubMed Abstract: Emergent resistance to all clinical antibiotics calls for the next generation of therapeutics. Here we report an effective antimicrobial strategy targeting the bacterial hydrogen sulfide (HS)-mediated defense system. We identified cystathionine γ-lyase (CSE) as the primary generator of HS in two major human pathogens, and , and discovered small molecules that inhibit bacterial CSE. These inhibitors potentiate bactericidal antibiotics against both pathogens in vitro and in mouse models of infection. CSE inhibitors also suppress bacterial tolerance, disrupting biofilm formation and substantially reducing the number of persister bacteria that survive antibiotic treatment. Our results establish bacterial HS as a multifunctional defense factor and CSE as a drug target for versatile antibiotic enhancers.

PubMed: 34112687
DOI: 10.1126/science.abd8377

実験手法

X-RAY DIFFRACTION (2.52 Å)