7MCU

Crystal structure of Staphylococcus aureus Cystathionine gamma lyase, Holoenzyme with bound NL2

Summary for 7MCU

• Entry DOI: 10.2210/pdb7mcu/pdb
• Descriptor: Bifunctional cystathionine gamma-lyase/homocysteine desulfhydrase, PYRIDOXAL-5'-PHOSPHATE, 5-[(6-bromo-1H-indol-1-yl)methyl]-2-methylfuran-3-carboxylic acid, ... (7 entities in total)
• Functional Keywords: amino-acid biosynthesis, cysteine biosynthesis, hydrogen sulfide production, plp dependent enzyme, lyase
• Biological source: Staphylococcus aureus
• Total number of polymer chains: 1
• Total formula weight: 42602.38

Authors

Nuthanakanti, A.,Serganov, A.,Kaushik, A. (deposition date: 2021-04-02, release date: 2021-06-23, Last modification date: 2023-11-15)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.4 Å)