Filling the gap of intracellular dephosphorylation in the Plasmodium falciparum vitamin B1 biosynthesis.
Thiamine pyrophosphate (TPP), the active form of vitamin B1, is an essential cofactor for several enzymes. Humans depend exclusively on the uptake of vitamin B1, whereas bacteria, plants, fungi and the malaria parasite Plasmodium falciparum are able to synthesise thiamine monophosphate (TMP) de novo. TMP has to be dephosphorylated prior to pyrophosphorylation in order to obtain TPP. In P. falciparum the phosphatase capable to catalyse this reaction has been identified by analysis of the substrate specificity. The recombinant enzyme accepts beside vitamin B1 also nucleotides, phosphorylated sugars and the B6 vitamer pyridoxal 5'-phosphate. Vitamin B1 biosynthesis is known to occur in the cytosol. The cytosolic localisation of this phosphatase was verified by transfection of a GFP chimera construct. Stage specific Northern blot analysis of the phosphatase clearly identified an expression profile throughout the entire erythrocytic life cycle of P. falciparum and thereby emphasises the importance of dephosphorylation reactions within the malaria parasite.
Knöckel
Julia
J
Bernhard Nocht Institute for Tropical Medicine, Department of Biochemistry, Bernhard Nocht Strasse 74, Hamburg, Germany.
Bergmann
Bärbel
B
Müller
Ingrid B
IB
Rathaur
Sushma
S
Walter
Rolf D
RD
Wrenger
Carsten
C
D009597:4-Nitrophenylphosphatase / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D003600:Cytosol / Q000737:chemistry; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D020869:Gene Expression Profiling; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009711:Nucleotides / Q000378:metabolism; D010963:Plasmodium falciparum / Q000201:enzymology*; D011730:Pyridoxal / Q000031:analogs & derivatives / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013379:Substrate Specificity; D013831:Thiamine / Q000378:metabolism; D013833:Thiamine Monophosphate / Q000378:metabolism*
D016054:DNA, Protozoan; D009711:Nucleotides; D011994:Recombinant Proteins; D011730:Pyridoxal; C036319:pyridoxal 5'-sulfate; D013833:Thiamine Monophosphate; D009597:4-Nitrophenylphosphatase; D013831:Thiamine