Exploring Intein Inhibition by Platinum Compounds as an Antimicrobial Strategy.

ABSTRACT: Inteins, self-splicing protein elements, interrupt genes and proteins in many microbes, including the human pathogen Mycobacterium tuberculosis Using conserved catalytic nucleophiles at their N- and C-terminal splice junctions, inteins are able to excise out of precursor polypeptides. The splicing of the intein in the mycobacterial recombinase RecA is specifically inhibited by the widely used cancer therapeutic cisplatin, cis-[Pt(NH₃)₂Cl₂], and this compound inhibits mycobacterial growth. Mass spectrometric and crystallographic studies of Pt(II) binding to the RecA intein revealed a complex in which two platinum atoms bind at N- and C-terminal catalytic cysteine residues. Kinetic analyses of NMR spectroscopic data support a two-step binding mechanism in whi

SUBMITTER: Chan H 

PROVIDER: S-EPMC5077202 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature