Download MendeleyVitamin B6 Biosynthesis by the Malaria Parasite Plasmodium falciparum: Biochemical and structural insights
Gengenbacher, M., Fitzpatrick, T.B., Raschle, T., Flicker, K., Sinning, I., Mueller, S., Macheroux, P., Tews, I., Kappes, B.(2006) J Biol Chem 281: 3633-3641
- PubMed: 16339145
- DOI: https://doi.org/10.1074/jbc.M508696200
- Primary Citation of Related Structures:
2ABW - 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.
Organizational Affiliation:
Abteilung für Parasitologie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 324, D-69120 Heidelberg, Germany.
