2mlm

Solution structure of sortase A from S. aureus in complex with benzo[d]isothiazol-3-one based inhibitor

spinqualitylabelsall models 2mlm Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2mlm is a 1 chain structure with sequence from Staphylococcus aureus CA-347. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR, 20 models Ligands: 2W7 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Gram-positive bacteria, in general, and staphylococci, in particular, are the widespread cause of nosocomial and community-acquired infections. The rapid evolvement of strains resistant to antibiotics currently in use is a serious challenge. Novel antimicrobial compounds have to be developed to fight these resistant bacteria, and sortase A, a bacterial cell wall enzyme, is a promising target for novel therapies. As a transpeptidase that covalently attaches various virulence factors to the cell surface, this enzyme plays a crucial role in the ability of bacteria to invade the host's tissues and to escape the immune response. In this study we have screened a small molecule library against recombinant Staphylococcus aureus sortase A using an in vitro FRET-based assay. The selected hits were validated by NMR methods in order to exclude false positives and to analyze the reversibility of inhibition. Further structural and functional analysis of the best hit allowed the identification of a novel class of benzisothiazolinone-based compounds as potent and promising sortase inhibitors. Discovery and structure-activity relationship studies of irreversible benzisothiazolinone-based inhibitors against Staphylococcus aureus sortase A transpeptidase.,Zhulenkovs D, Rudevica Z, Jaudzems K, Turks M, Leonchiks A Bioorg Med Chem. 2014 Sep 16. pii: S0968-0896(14)00647-6. doi:, 10.1016/j.bmc.2014.09.011. PMID:25282649 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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