2ok7
From Proteopedia
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Ferredoxin-NADP+ reductase from Plasmodium falciparum with 2'P-AMP
Overview
The completion of the Plasmodium falciparum genome sequence has recently, promoted the search for new antimalarial drugs. More specifically, metabolic pathways of the apicoplast, a key organelle for survival of the, parasite, have been recognized as potential targets for the development of, specific new antimalarial agents. As most apicomplexan parasites, P., falciparum displays a plant-type ferredoxin-NADP(+) reductase, yielding, reduced ferredoxin for essential biosynthetic pathways in the apicoplast., Here we report a molecular, kinetic and ligand binding characterization of, the recombinant ferredoxin-NADP(+) reductase from P. falciparum, in the, light of current data available for plant ferredoxin-NADP(+) reductases., In parallel with the functional characterization, we describe the crystal, structures of P. falciparum ferredoxin-NADP(+) reductase in free form and, in complex with 2'-phospho-AMP (at 2.4 and 2.7 A resolution, respectively). The enzyme displays structural properties likely to be, unique to plasmodial reductases. In particular, the two crystal structures, highlight a covalent dimer, which relies on the oxidation of residue Cys99, in two opposing subunits, and a helix-coil transition that occurs in the, NADP-binding domain, triggered by 2'-phospho-AMP binding. Studies in, solution show that NADP(+), as well as 2'-phospho-AMP, promotes the, formation of the disulfide-stabilized dimer. The isolated dimer is, essentially inactive, but full activity is recovered upon disulfide, reduction. The occurrence of residues unique to the plasmodial enzyme, and, the discovery of specific conformational properties, highlight the, NADP-binding domain of P. falciparum ferredoxin-NADP(+) reductase as, particularly suited for the rational development of antimalarial, compounds.
About this Structure
2OK7 is a Single protein structure of sequence from Plasmodium falciparum with , and as ligands. Active as Ferredoxin--NADP(+) reductase, with EC number 1.18.1.2 Full crystallographic information is available from OCA.
Reference
Ferredoxin-NADP(+) Reductase from Plasmodium falciparum Undergoes NADP(+)-dependent Dimerization and Inactivation: Functional and Crystallographic Analysis., Milani M, Balconi E, Aliverti A, Mastrangelo E, Seeber F, Bolognesi M, Zanetti G, J Mol Biol. 2007 Mar 23;367(2):501-13. Epub 2007 Jan 9. PMID:17258767
Page seeded by OCA on Tue Jan 29 21:12:17 2008
