Wednesday, October 24, 2018

Celastrol binds to its target protein via specific noncovalent interactions and reversible covalent bond

Duo Zhang, Ziwen Chen, Caocao Hu, Siwei Yan, Zhuoer Li, Baohuan Lian, Yang Xu, Ding Rong, Zhiping Zeng, Xiao-kun Zhang and Ying Su

Chem. Commun., 2018
DOI: 10.1039/C8CC06140H

Celastrol is one of the most studied natural products. Our studies show for the first time that celastrol can bind to its target protein via specific noncovalent interactions, that position celastrol next to the thiol group of the reactive cysteine for reversible covalent bond formation. Such specific noncovalent interactions confer celastrol’s binding specificity and demonstrate the feasibility of improving the efficacy and selectivity of celastrol for therapeutic application.
Celastrol.svg

Oncogenic KRAS G12C: Kinetic and Redox Characterization of Covalent Inhibition

Minh V. Huynh, Derek Parsonage, Tom E. Forshaw, Venkat R. Chirasani, G. Aaron Hobbs, Hanzhi Wu, Jingyun Lee, Cristina M. Furdui, Leslie B. P...