Increasing the distance between two monomers of topoisomerase IIβ under the action of antitumor agent 4β-sulfur-(benzimidazole) 4'-demethylepipodophyllotoxin.

ABSTRACT: Topoisomerases II (Top2s) are a group of essential enzymes involved in replication, transcription, chromosome condensation, and segregation via altering DNA topology. The mechanism of the Top2s poisons such as etoposide (VP-16) was reported as stabilizing the Top2-DNA complex and engendering permanent DNA breakage. As the structurally similar compound of VP-16, a novel 4β-sulfur-substituted 4'-demethylepipodophyllotoxin (DMEP) derivative (compound C-Bi) with superior antitumor activity was developed in our previous study. To understand the structural basis of the compound action, the crystal structure (2.54 Å) of human Top2 β-isoform (hTop2β) cleavage complexes stabilized by compound C-Bi was determined. However, compound C-Bi was not visible in the crystal structure. Through the compariso

SUBMITTER: Sun LY 

PROVIDER: S-EPMC6175940 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature