2o2y
|
The crystal structure of P. falciparum enoyl acyl carrier protein reductase
OverviewOverview
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, apicomplexan family that flanks the substrate-binding domain and is, disordered in all other reported apicomplexan ENR structures. Structural, comparison of the apicomplexan ENR structures with their bacterial and, plant counterparts has revealed that although the active sites of the, parasite enzymes are broadly similar to those of their bacterial, counterparts, there are a number of important differences within the, drug-binding pocket that reduce the packing interactions formed with, several inhibitors in the apicomplexan ENR enzymes. Together with other, significant structural differences, this provides a possible explanation, of the lower affinity of the parasite ENR enzyme family for, aminopyridine-based inhibitors, suggesting that an effective antiparasitic, agent may well be distinct from equivalent antimicrobials.
About this StructureAbout this Structure
2O2Y is a Single protein structure of sequence from Plasmodium falciparum with , , and as ligands. Active as [acyl-carrier-protein_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number 1.3.1.9 Full crystallographic information is available from OCA.
ReferenceReference
Studies of Toxoplasma gondii and Plasmodium falciparum enoyl acyl carrier protein reductase and implications for the development of antiparasitic agents., Muench SP, Prigge ST, McLeod R, Rafferty JB, Kirisits MJ, Roberts CW, Mui EJ, Rice DW, Acta Crystallogr D Biol Crystallogr. 2007 Mar;63(Pt 3):328-38. Epub 2007, Feb 21. PMID:17327670 [[Category: Enoyl-[acyl-carrier-protein] reductase (NADH)]]
Page seeded by OCA on Tue Jan 29 21:04:17 2008