2MLM
Solution structure of sortase A from S. aureus in complex with benzo[d]isothiazol-3-one based inhibitor
Summary for 2MLM
| Entry DOI | 10.2210/pdb2mlm/pdb |
| NMR Information | BMRB: 19826 |
| Descriptor | Sortase family protein, N-{2-oxo-2-[(3s,5s,7s)-tricyclo[3.3.1.1~3,7~]dec-1-ylamino]ethyl}-2-sulfanylbenzamide (2 entities in total) |
| Functional Keywords | hydrolase/hydrolase inhibitor, hydrolase-hydrolase inhibitor complex |
| Biological source | Staphylococcus aureus |
| Total number of polymer chains | 1 |
| Total formula weight | 17169.53 |
| Authors | Jaudzems, K.,Zhulenkovs, D.,Leonchiks, A. (deposition date: 2014-03-03, release date: 2014-11-19, Last modification date: 2024-10-30) |
| Primary citation | Zhulenkovs, D.,Rudevica, Z.,Jaudzems, K.,Turks, M.,Leonchiks, A. Discovery and structure-activity relationship studies of irreversible benzisothiazolinone-based inhibitors against Staphylococcus aureus sortase A transpeptidase. Bioorg.Med.Chem., 22:5988-6003, 2014 Cited by PubMed Abstract: 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. PubMed: 25282649DOI: 10.1016/j.bmc.2014.09.011 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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