7V6K

Crystal structure of Sortase A from Streptococcus pyogenes in complex with ML346

Summary for 7V6K

• Entry DOI: 10.2210/pdb7v6k/pdb
• Descriptor: Sortase, 5-[3-(4-methoxyphenyl)prop-2-enylidene]-1,3-diazinane-2,4,6-trione, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: sortase a, transpetidase, hydrolase
• Biological source: Streptococcus pyogenes
• Total number of polymer chains: 2
• Total formula weight: 42116.49

Authors

Yang, C.G.,Gan, J. (deposition date: 2021-08-20, release date: 2021-12-29, Last modification date: 2024-11-20)

Primary citation

Guan, X.N.,Zhang, T.,Yang, T.,Dong, Z.,Yang, S.,Lan, L.,Gan, J.,Yang, C.G.
Covalent sortase A inhibitor ML346 prevents Staphylococcus aureus infection of Galleria mellonella.
Rsc Med Chem, 13:138-149, 2022

PubMed Abstract: The housekeeping sortase A (SrtA), a membrane-associated cysteine transpeptidase, is responsible for anchoring surface proteins to the cell wall peptidoglycan in Gram-positive bacteria. This process is essential for the regulation of bacterial virulence and pathogenicity. Therefore, SrtA is considered to be an ideal target for antivirulence therapy. In this study, we report that ML346, a compound with a barbituric acid and cinnamaldehyde scaffold, functions as an irreversible inhibitor of SrtA (SrtA) and SrtA (SrtA) at low micromolar concentrations. According to our X-ray crystal structure of the SrtA/ML346 complex (Protein Data Bank ID: 7V6K), ML346 covalently modifies the thiol group of Cys208 in the active site of SrtA. Importantly, ML346 significantly attenuated the virulence phenotypes of and exhibited inhibitory effects on larva infection caused by . Collectively, our results indicate that ML346 has potential for development as a covalent antivirulence agent for treating infections, including methicillin-resistant .

PubMed: 35308030
DOI: 10.1039/d1md00316j

Experimental method

X-RAY DIFFRACTION (1.57 Å)