Aspartic proteases of Plasmodium falciparum and other parasitic protozoa as drug targets.
All parasitic protozoa contain multiple proteases, some of which are attracting attention as drug targets. Aspartic proteases are already the targets of some clinically useful drugs (e.g. chemotherapy of HIV infection) and a variety of factors make these enzymes appealing to those seeking novel antiparasite therapies. This review provides a critical analysis of the current knowledge on Plasmodium aspartic proteases termed plasmepsins, proposes a definitive nomenclature for this group of enzymes, and compares these enzymes with aspartic proteases of humans and other parasitic protozoa. The present status of attempts to obtain specific inhibitors of the parasite enzymes that will be useful as drugs is outlined and suggestions for future research priorities are proposed.
Coombs
G H
GH
University of Glasgow, G12 8QQ, Glasgow, UK. g.coombs@bio.gla.ac.uk
Goldberg
D E
DE
Klemba
M
M
Berry
C
C
Kay
J
J
Mottram
J C
JC
D000595:Amino Acid Sequence; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016282:Aspartic Acid Endopeptidases / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D056890:Eukaryota / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D016133:Polymerase Chain Reaction; D011528:Protozoan Infections / Q000188:drug therapy; D016415:Sequence Alignment; D017385:Sequence Homology
D000981:Antiprotozoal Agents; D016282:Aspartic Acid Endopeptidases; C089643:plasmepsin