5HU4
Cystal structure of listeria monocytogenes sortase A
Summary for 5HU4
| Entry DOI | 10.2210/pdb5hu4/pdb |
| Descriptor | Cysteine protease (2 entities in total) |
| Functional Keywords | protease, sortase a, hydrolase |
| Biological source | Listeria monocytogenes |
| Total number of polymer chains | 1 |
| Total formula weight | 16113.42 |
| Authors | |
| Primary citation | Li, H.,Chen, Y.,Zhang, B.,Niu, X.,Song, M.,Luo, Z.,Lu, G.,Liu, B.,Zhao, X.,Wang, J.,Deng, X. Inhibition of sortase A by chalcone prevents Listeria monocytogenes infection. Biochem. Pharmacol., 106:19-29, 2016 Cited by PubMed Abstract: The critical role of sortase A in gram-positive bacterial pathogenicity makes this protein a good potential target for antimicrobial therapy. In this study, we report for the first time the crystal structure of Listeria monocytogenes sortase A and identify the active sites that mediate its transpeptidase activity. We also used a sortase A (SrtA) enzyme activity inhibition assay, simulation, and isothermal titration calorimetry analysis to discover that chalcone, an agent with little anti-L. monocytogenes activity, could significantly inhibit sortase A activity with an IC50 of 28.41 ± 5.34 μM by occupying the active site of SrtA. The addition of chalcone to a co-culture of L. monocytogenes and Caco-2 cells significantly inhibited bacterial entry into the cells and L. monocytogenes-mediated cytotoxicity. Additionally, chalcone treatment decreased the mortality of infected mice, the bacterial burden in target organs, and the pathological damage to L. monocytogenes-infected mice. In conclusion, these findings suggest that chalcone is a promising candidate for the development of treatment against L. monocytogenes infection. PubMed: 26826492DOI: 10.1016/j.bcp.2016.01.018 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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