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Vitamin B6 biosynthesis by the malaria parasite Plasmodium falciparum: biochemical and structural insights |
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Authors | ![]() | |
Published in | The Journal of biological chemistry. 2006, vol. 281, no. 6, p. 3633-3641 | |
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. | |
Keywords | Animals — Antigens — Protozoan/chemistry — Bacillus subtilis/metabolism — Blotting — Western — Catalysis — Catalytic Domain — Cloning — Molecular — Crystallography — X-Ray — Databases as Topic — Electrophoresis — Polyacrylamide Gel — Genetic Complementation Test — Glutaminase/chemistry/metabolism — Immunoblotting — Ions — Malaria/parasitology — Models — Molecular — Molecular Sequence Data — Oligonucleotides/chemistry — Plasmodium falciparum/metabolism — Protein Binding — Protein Conformation — Protein Structure — Tertiary — Protozoan Proteins/chemistry — Recombinant Proteins/chemistry — Time Factors — Vitamin B 6/biosynthesis/chemistry | |
Identifiers | PMID: 16339145 | |
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Citation (ISO format) | GENGENBACHER, Martin et al. Vitamin B6 biosynthesis by the malaria parasite Plasmodium falciparum: biochemical and structural insights. In: The Journal of biological chemistry, 2006, vol. 281, n° 6, p. 3633-3641. doi: 10.1074/jbc.M508696200 https://archive-ouverte.unige.ch/unige:89536 |