5LIR

Structure of the SALTY Sigma cross-reacting protein 27A (SCRP-27A) from Salmonella typhimurium

Summary for 5LIR

• Entry DOI: 10.2210/pdb5lir/pdb
• Descriptor: Sigma cross-reacting protein 27A (SCRP-27A), DI(HYDROXYETHYL)ETHER (3 entities in total)
• Functional Keywords: rossmann fold class i glutamine amidotransferase-like, transferase
• Biological source: Salmonella enterica subsp. enterica serovar Typhimurium
• Total number of polymer chains: 1
• Total formula weight: 25944.70

Authors

Schneider, S.,Mandel, M.,Sieber, S.A. (deposition date: 2016-07-15, release date: 2016-09-14, Last modification date: 2024-11-20)

Primary citation

Mandl, F.A.,Kirsch, V.C.,Ugur, I.,Kunold, E.,Vomacka, J.,Fetzer, C.,Schneider, S.,Richter, K.,Fuchs, T.M.,Antes, I.,Sieber, S.A.
Natural-Product-Inspired Aminoepoxybenzoquinones Kill Members of the Gram-Negative Pathogen Salmonella by Attenuating Cellular Stress Response.
Angew.Chem.Int.Ed.Engl., 55:14852-14857, 2016

PubMed Abstract: Gram-negative bacteria represent a challenging task for antibacterial drug discovery owing to their impermeable cell membrane and restricted uptake of small molecules. We herein describe the synthesis of natural-product-derived epoxycyclohexenones and explore their antibiotic activity against several pathogenic bacteria. A compound with activity against Salmonella Typhimurium was identified, and the target enzymes were unraveled by quantitative chemical proteomics. Importantly, two protein hits were linked to bacterial stress response, and corresponding assays revealed an elevated susceptibility to reactive oxygen species upon compound treatment. The consolidated inhibition of these targets provides a rationale for antibacterial activity and highlights epoxycyclohexenones as natural product scaffolds with suitable properties for killing Gram-negative Salmonella.

PubMed: 27782347
DOI: 10.1002/anie.201607338

Experimental method

X-RAY DIFFRACTION (1.75 Å)