This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
5hu4
From Proteopedia
Cystal structure of listeria monocytogenes sortase A
Structural highlights
FunctionSRTA_LISMO Transpeptidase that anchors surface proteins to the cell wall (PubMed:11854224, PubMed:11929538, PubMed:16247833, PubMed:22837151). Recognizes and modifies its substrate by proteolytic cleavage of a C-terminal sorting signal. Following cleavage, a covalent intermediate is formed via a thioester bond between the sortase and its substrate, which is then transferred and covalently attached to the cell wall (Probable). This sortase recognizes a Leu-Pro-x-Thr-Gly (LPXTG) motif, which is cleaved by the sortase between the threonine and glycine residues (PubMed:11929538). Involved in pathogenesis (PubMed:11854224, PubMed:11929538, PubMed:15028680). May regulate the rate of synthesis and/or the stability of a subset of LPXTG proteins (PubMed:22837151). Not involved in cell wall-anchoring of Hbp2 (SvpA) or Hbp1 (PubMed:15028680, PubMed:16247833).[1] [2] [3] [4] [5] [6] Publication Abstract from PubMedThe 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 muM 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. Inhibition of sortase A by chalcone prevents Listeria monocytogenes infection.,Li H, Chen Y, Zhang B, Niu X, Song M, Luo Z, Lu G, Liu B, Zhao X, Wang J, Deng X Biochem Pharmacol. 2016 Apr 15;106:19-29. doi: 10.1016/j.bcp.2016.01.018. Epub, 2016 Jan 28. PMID:26826492[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||
