Plasmodium falciparum neutral aminopeptidases: new targets for anti-malarials.
The neutral aminopeptidases M1 alanyl aminopeptidase (PfM1AAP) and M17 leucine aminopeptidase (PfM17LAP) of the human malaria parasite Plasmodium falciparum are targets for the development of novel anti-malarial drugs. Although the functions of these enzymes remain unknown, they are believed to act in the terminal stages of haemoglobin degradation, generating amino acids essential for parasite growth and development. Inhibitors of both enzymes are lethal to P. falciparum in culture and kill the murine malaria P. chabaudi in vivo. Recent biochemical, structural and functional studies provide the substrate specificity and mechanistic binding data needed to guide the development of more potent anti-malarial drugs. Together with biological studies, these data form the rationale for choosing PfM1AAP and PfM17LAP as targets for anti-malarial development.
Skinner-Adams
Tina S
TS
Malaria Biology Laboratory, Queensland Institute of Medical Research, Herston, QLD 4006, Australia. tinas@qimr.edu.au
Stack
Colin M
CM
Trenholme
Katharine R
KR
Brown
Chris L
CL
Grembecka
Jolanta
J
Lowther
Jonathan
J
Mucha
Artur
A
Drag
Marcin
M
Kafarski
Pawel
P
McGowan
Sheena
S
Whisstock
James C
JC
Gardiner
Donald L
DL
Dalton
John P
JP
D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D000962:Antimalarials / Q000494:pharmacology*; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000503:physiopathology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology
D000962:Antimalarials; D000626:Aminopeptidases