Congopain from Trypanosoma congolense: drug target and vaccine candidate.
Trypanosomes are the etiological agents of human sleeping sickness and livestock trypanosomosis (nagana), which are major diseases in Africa. Their cysteine proteases (CPs), which are members of the papain family, are expressed during the infective stages of the parasites' life cycle. They are suspected to act as pathogenic factors in the mammalian host, where they also trigger prominent immune responses. Trypanosoma congolense, a major pathogenic species in livestock, possesses at least two families of closely related CPs, named CP1 and CP2. Congopain, a CP2-type of enzyme, shares structural and functional resemblances with cruzipain from T. cruzi and with mammalian cathepsin L. Like CPs from other Trypanosomatids, congopain might be an attractive target for trypanocidal drugs. Here we summarise the current knowledge in the two main areas of research on congopain: first, the biochemical properties of congopain were characterised and its substrate specificity was determined, as a first step towards drug design; second, the possibility was being explored that inhibition of congopain by host-specific antibodies may mitigate the pathology associated with trypanosome infection.
Lalmanach
Gilles
G
Laboratoire d'Enzymologie et Chimie des Protéines, INSERM EMI-U 00.10, Université François Rabelais, Faculté de Médecine, Tours, France.
Boulangé
Alain
A
Serveau
Carole
C
Lecaille
Fabien
F
Scharfstein
Julio
J
Gauthier
Francis
F
Authié
Edith
E
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D020134:Catalytic Domain; D002417:Cattle; D002418:Cattle Diseases / Q000276:immunology / Q000469:parasitology*; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D015195:Drug Design; D007114:Immunization / Q000662:veterinary; D016052:Protozoan Vaccines / Q000276:immunology; D013379:Substrate Specificity; D014348:Trypanosoma congolense / Q000201:enzymology*; D014353:Trypanosomiasis, African / Q000097:blood / Q000276:immunology* / Q000469:parasitology
D000913:Antibodies, Protozoan; D016052:Protozoan Vaccines; D003546:Cysteine Endopeptidases; C084086:congopain