The gene of an NADP+-specific glutamate dehydrogenase was cloned from Plasmodium 
falciparum, the causative agent of tropical malaria. Southern-blot analysis 
indicates a single-copy gene. The gene encodes a protein with 470 residues which 
has 50% of all residues identical with those of the glutamate dehydrogenases 
from other low eukaryotes and eubacteria. In contrast, the sequence identity 
with the human enzyme is marginal, which underlines the long evolutionary 
distance between parasite and host. The gene was overexpressed in Escherichia 
coli. The kinetic properties of the recombinant enzyme are in good agreement 
with those of the authentic enzyme. The parasite enzyme is inhibited by 
D-glutamate and glutarate, but not by chloroquine. Like other coenzyme-specific 
glutamate dehydrogenases, but in contrast to the dual-specific mammalian 
enzymes, the P. falciparum enzyme is not affected by GTP and ADP. The physical 
and chemical properties of the protein are in accordance with the cytosol being 
the major localization. The gene does not encode a cleavable mitochondrial 
presequence and the Mr of the recombinant protein and the protein isolated from 
the parasite are indistinguishable on SDS/PAGE. Western-blot analysis of 
stage-specific parasites shows that glutamate dehydrogenase is present in all 
intraerythrocytic stages. The signal increased continuously from rings, early 
trophozoites to late trophozoites and decreased slightly in the segmenter stage. 
Glutamate dehydrogenase, suggested to be the major source of NADPH in the 
parasite, is an attractive target molecule for the rational development of new 
antimalarial drugs.