Screening of curcumin analogues targeting Sortase A enzyme of Enterococcus faecalis: a molecular dynamics approach

• Published in: Journal of proteins and proteomics 2019-09, Vol.10 (3), p.245-255
• Main Authors: Sivaramakrishnan, Muthusaravanan, Sharavanan, Vivek Jagadeesan, Durairaj, D. Ruban, Kandaswamy, Kumaravel, Piramanayagam, Shanmughavel, Kothandan, Ram
• Format: Article
• Language: English
• Subjects: Biological and Medical Physics; Biomedical and Life Sciences; Biomedical Engineering/Biotechnology; Biomedicine; Biophysics; Cell Biology; Medicinal Chemistry; Original Article; Proteomics; Systems Biology
• ISSN: 0975-8151; 2524-4663
• DOI: 10.1007/s42485-019-00020-y

This study is aimed to determine the 3D structure of a bacterial virulence protein Sortase A (SrtA) and to screen for curcumin analogues with high bioavailability and drug like properties that can target SrtA. SrtA is a membrane anchored protein, crucial for efficient pilus assembly, biofilm formation, and colonization of host tissue. Therefore, in this study SrtA was chosen as an antimicrobial target. However, lack of crystallography structural data of Enterococcus faecalis ( E. faecalis ) SrtA was a major shortcoming in screening for antimicrobial compounds. Therefore, in this work, we have elucidated the 3D structure of SrtA of E. faecalis using homology modeling. In addition, the molecular docking study confirmed that the curcumin analogue CA51 had better binding activity towards SrtA. Furthermore, the analogue CA51 was bound to the active site of SrtA enzyme in a stable conformation throughout the simulation time scale of 10 ns. From the molecular dynamics results, we propose that the analogue CA51 is a potent inhibitor of E. faecalis SrtA and can be used as novel antimicrobial compound against E. faecalis infections.