The high ‐resolution X‐ray structure of vinca‐domain inhibitors of microtubules provides a rational approach for drug design

In this study, we determined the high‐resolution crystal structures of vinorelbine, YXD, and Phomopsin A in complex with tubulin at 2.5 Å. Additionally, we recapitulated all previously published high‐resolution crystal structures of the vinca binding site to reveal critical residues and the molecular mechanism of vinca‐ domain ligands interacting with tubulin. Furthermore, we designed putatively novel triazolopyrimidine derivatives by introducing secondary amine groups to establish salt‐bridge and H‐bond interactions with Asp179β1 and Asn329α2. Our studies provided the structural basis for designing novel tubulin vinca ‐domain ligands.

Source: FEBS Letters - January 10, 2021 Category: Biochemistry Authors: Wu Chengyong, Xian Jinghong, Wang Yanyan, Xiao Qing ‐Jie, Ma Lingling, Li Yuyan, Chen Hai, Lei Qian, Zhang Quan, Sun Bo, Wang Yuxi Tags: Research Article Source Type: research