Studies of Toxoplasma gondii and Plasmodium falciparum enoyl acyl carrier protein reductase and implications for the development of antiparasitic agents.

ABSTRACT: Recent studies have demonstrated that submicromolar concentrations of the biocide triclosan arrest the growth of the apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii and inhibit the activity of the apicomplexan enoyl acyl carrier protein reductase (ENR). The crystal structures of T. gondii and P. falciparum ENR in complex with NAD(+) and triclosan and of T. gondii ENR in an apo form have been solved to 2.6, 2.2 and 2.8 A, respectively. The structures of T. gondii ENR have revealed that, as in its bacterial and plant homologues, a loop region which flanks the active site becomes ordered upon inhibitor binding, resulting in the slow tight binding of triclosan. In addition, the T. gondii ENR-triclosan complex reveals the folding of a hydrophilic insert common to the apicompl

SUBMITTER: Muench SP 

PROVIDER: S-EPMC2483495 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature