Vitamin B6 biosynthesis by the malaria parasite Plasmodium falciparum: biochemical and structural insights.
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Gengenbacher M, Fitzpatrick TB, Raschle T, Flicker K, Sinning I, Muller S, Macheroux P, Tews I, Kappes B
Vitamin B6 biosynthesis by the malaria parasite Plasmodium falciparum: biochemical and structural insights.
J Biol Chem. 2006 Feb 10;281(6):3633-41. doi: 10.1074/jbc.M508696200. Epub 2005 Dec 8.
- PubMed ID
- 16339145 [ View in PubMed]
- Abstract
Vitamin B6 is one of nature's most versatile cofactors. Most organisms synthesize vitamin B6 via a recently discovered pathway employing the proteins Pdx1 and Pdx2. Here we present an in-depth characterization of the respective orthologs from the malaria parasite, Plasmodium falciparum. Expression profiling of Pdx1 and -2 shows that blood-stage parasites indeed possess a functional vitamin B6 de novo biosynthesis. Recombinant Pdx1 and Pdx2 form a complex that functions as a glutamine amidotransferase with Pdx2 as the glutaminase and Pdx1 as pyridoxal-5 '-phosphate synthase domain. Complex formation is required for catalytic activity of either domain. Pdx1 forms a chimeric bi-enzyme with the bacterial YaaE, a Pdx2 ortholog, both in vivo and in vitro, although this chimera does not attain full catalytic activity, emphasizing that species-specific structural features govern the interaction between the protein partners of the PLP synthase complexes in different organisms. To gain insight into the activation mechanism of the parasite bi-enzyme complex, the three-dimensional structure of Pdx2 was determined at 1.62 A. The obstruction of the oxyanion hole indicates that Pdx2 is in a resting state and that activation occurs upon Pdx1-Pdx2 complex formation.