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Inhibition of human DNA topoisomerase IB by a cyclometalated gold III compound: analysis on the different steps of the enzyme catalytic cycle.

Abstract：

:A gold(III) compound [Au(C^N^C)(IMe)]CF(3)SO(3) (Gold III) has been reported to have anticancer properties as it is able to reduce topoisomerase IB activity in vitro and suppress tumor growth in nude mice model. Here we have investigated the mechanism of inhibition of human topoisomerase IB activity by this compound, analyzing the various steps of the catalytic cycle. DNA supercoiled relaxation and the cleavage reaction are inhibited, but Gold III does not perturb the religation reaction, in contrast to what has been observed for camptothecin. Pre-incubation of enzyme with the inhibitor before adding DNA substrate increases the inhibitory effect. In addition, when Gold III is preincubated with the enzyme it prevents the stabilization of the cleavable complex by camptothecin. The analysis of the DNA-topoisomerase binding reaction indicates that the compound acts as a topoisomerase I inhibitor by preventing the enzyme-DNA interaction.

journal_name

Arch Biochem Biophys

journal_title

Archives of biochemistry and biophysics

authors

Castelli S,Vassallo O,Katkar P,Che CM,Sun RW,Desideri A

doi

10.1016/j.abb.2011.10.008

subject

Has Abstract

pub_date

2011-12-15 00:00:00

pages

108-12

issue

2

eissn

0003-9861

issn

1096-0384

pii

S0003-9861(11)00345-6

journal_volume

516

pub_type

杂志文章

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