The genome of Plasmodium falciparum encodes an active delta-aminolevulinic acid dehydratase.
The enzyme delta-aminolevulinic acid dehydratase (ALAD) catalyses the second reaction in the heme biosynthetic pathway. It has been suggested previously that the malaria parasite Plasmodium falciparum imports this enzyme from the host cell for de novo heme biosynthesis. However, the parasite's genome encodes an orthologue for ALAD. Here we report molecular cloning of a complete cDNA for the parasite's intrinsic ALAD and show it rescues an ALAD-null mutant of Escherichia coli, indicating that the malarial gene encodes a functional ALAD. The malarial ALAD has a long bipartite extension at its N-terminus, which may function as a plastid targeting signal. The amino acid sequence of the enzyme is related most closely to those of plant/algal chloroplast ALADs, though the malarial version may lack the allosteric Mg2+-binding site, which is conserved among chloroplast ALADs.
Sato
Shigeharu
S
Division of Parasitology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK. ssato@nimr.mrc.ac.uk
Wilson
R J M
RJ
D000495:Allosteric Site; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D005816:Genetic Complementation Test; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D010944:Plants / Q000201:enzymology; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000235:genetics*; D000623:Porphobilinogen Synthase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
D000623:Porphobilinogen Synthase