Recovery of the poisoned topoisomerase II for DNA religation: coordinated motion of the cleavage core revealed with the microsecond atomistic simulation.

ABSTRACT: Type II topoisomerases resolve topological problems of DNA double helices by passing one duplex through the reversible double-stranded break they generated on another duplex. Despite the wealth of information in the cleaving operation, molecular understanding of the enzymatic DNA ligation remains elusive. Topoisomerase poisons are widely used in anti-cancer and anti-bacterial therapy and have been employed to entrap the intermediates of topoisomerase IIβ with religatable DNA substrate. We removed drug molecules from the structure and conducted molecular dynamics simulations to investigate the enzyme-mediated DNA religation. The drug-unbound intermediate displayed transitions toward the resealing-compliant configuration: closing distance between the cleaved DNA termini, B-to-A transformatio

SUBMITTER: Huang NL 

PROVIDER: S-EPMC4538842 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature