Plasmodium falciparum is the main causative agent of tropical malaria, the most 
severe parasitic disease in the world. Growing resistance of Plasmodia towards 
available drugs is an increasing problem in countries where malaria is endemic. 
As Plasmodia are sensitive to oxidative stress, augmenting this in the parasite 
represents a promising principle for the development of novel antimalarial 
drugs. The NADP-dependent glutamate dehydrogenase (GDH) of P.falciparum is 
largely responsible for the production of NADPH in the parasite, which in turn 
serves as electron source for the antioxidative enzymes glutathione reductase 
and thioredoxin reductase. As GDH does not occur in the host erythrocyte, GDH is 
a particularly attractive target for drug therapy. The three-dimensional 
structure of P.falciparum GDH in the unligated state has been determined by 
X-ray crystallography to a resolution of 2.7A. Compared to the mammalian 
enzymes, two amino acid residues are exchanged in the putative active site of 
the parasite GDH. The most obvious differences between parasite and human GDH 
are the subunit interfaces of the hexameric proteins. In the parasite protein, 
several salt-bridges mediate contacts between the subunits whereas in the human 
enzyme these interactions are mainly of hydrophobic nature. Furthermore, 
P.falciparum GDH possesses a unique N-terminal extension that does not occur in 
any other GDH sequence so far studied. These findings might be exploited for the 
design of peptidomimetics capable of disrupting the oligomeric organisation of 
the parasite enzyme.