Cisplatin inhibits protein splicing, suggesting inteins as therapeutic targets in mycobacteria.

ABSTRACT: Mycobacterium tuberculosis harbors three protein splicing elements, called inteins, in critical genes and their protein products. Post-translational removal of the inteins occurs autocatalytically and is required for function of the respective M. tuberculosis proteins. Inteins are therefore potential targets for antimycobacterial agents. In this work, we report that the splicing activity of the intein present in the RecA recombinase of M. tuberculosis is potently inhibited by the anticancer drug cisplatin (cis-diamminedichloro-platinum(II)). This previously unrecognized activity of cisplatin was established using both an in vitro intein splicing assay, which yielded an IC(50) of ∼2 μM, and a genetic reporter for intein splicing in Escherichia coli. Testing of related platinum(II) complexes

SUBMITTER: Zhang L 

PROVIDER: S-EPMC3020735 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature