7v6k | pdb_00007v6k

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

spinqualitylabelsall models 7v6k, resolution 1.57Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7v6k is a 2 chain structure with sequence from Streptococcus pyogenes. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.57Å Ligands: 5TI, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q99ZN4_STRP1 Publication Abstract from PubMed 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 Staphylococcus aureus SrtA (SaSrtA) and Streptococcus pyogenes SrtA (SpSrtA) in vitro at low micromolar concentrations. According to our X-ray crystal structure of the SpSrtADeltaN81/ML346 complex (Protein Data Bank ID: 7V6K), ML346 covalently modifies the thiol group of Cys208 in the active site of SpSrtA. Importantly, ML346 significantly attenuated the virulence phenotypes of S. aureus and exhibited inhibitory effects on Galleria mellonella larva infection caused by S. aureus. Collectively, our results indicate that ML346 has potential for development as a covalent antivirulence agent for treating S. aureus infections, including methicillin-resistant S. aureus. Covalent sortase A inhibitor ML346 prevents Staphylococcus aureus infection of Galleria mellonella.,Guan XN, Zhang T, Yang T, Dong Z, Yang S, Lan L, Gan J, Yang CG RSC Med Chem. 2021 Nov 1;13(2):138-149. doi: 10.1039/d1md00316j. eCollection 2022, Feb 23. PMID:35308030 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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