Mechanism of Phytochemicals : Affects the Polymerization and Depolymerisation of Actins

June 24, 2020by admin

Mechanical understanding of the correlation between actin assembly and ATP hydrolysis has been an object of intensive studies in biochemistry and structural biology. Azadirachtin(A) (AZA), a potential insecticide from neem, binds to actin and induces depolymerization in Drosophila. AZA binds to the pocket the same as that of Latrunculin A (LAT), but LAT inhibits actin polymerization by stiffening the actin structure and affects the ADP-ATP exchange. Cucurbitacin E (CurE) modulates the actin cytoskeleton by forming an irreversible covalent bond with Cys257 of actin. The reported binding conformation of CurE is deeply buried in the subdomain 4 of actin and is closely situated to the ATP-binding site. CurE allosterically modulates ADP and stabilizes the F-actin structure, affecting the nucleotide exchange and depolymerization of F-actin.

1. Roopa, L., Akshai, P. S., & Pravin Kumar, R. (2019). Connecting the dots in the mechanism of action of Cucurbitacin E (CurE) – path analysis and steered molecular dynamics reveal the precise site of entry and the passage of CurE in filamentous actin. Journal of Biomolecular Structure and Dynamics, 38(3), 635–646.
2. Kumar, R. P., Roopa, L., Nongthomba, U., Sudheer Mohammed, M. M., & Kulkarni, N. (2016). Docking, molecular dynamics, and QM/MM studies delineate the mode of binding of CucurbitacinE to F-actin. Journal of Molecular Graphics and Modelling, 63, 29–37.
3. L, R., R, P. K., & M.M., S. M. (2016). Molecular dynamics and high throughput binding free energy calculation of anti-actin anticancer drugs—New insights for better design. Computational Biology and Chemistry, 64, 47–55.
4. Kumar, R. P., Roopa, L., Mohammed, M. M., & Kulkarni, N. (2015). Azadirachtin(A) Distinctively Modulates Subdomain 2 of Actin – Novel Mechanism to Induce Depolymerization revealed by Molecular Dynamics Study. Journal of Biomolecular Structure and Dynamics, 1–39.