A fragment of the major histocompatibility complex class II-associated p41 invariant chain inhibits cruzipain, the major cysteine proteinase from Trypanosoma cruzi.
A peptide fragment derived from the p41 form of the invariant chain (Ii) associated with the major histocompatibility complex (MHC) class II molecule has been shown to inhibit the mammalian lysosomal cysteine proteinase, cathepsin L, and to be a novel cysteine proteinase inhibitor, distinct from cystatins. Here we report that this same fragment also binds to and inhibits cruzipain, the cathepsin L-like enzyme from the protozoan parasite Trypanosoma cruzi. The binding of the Ii fragment to cruzipain is fast (k(ass) = 2.4 x 10(7) M(-1) s(-1) and tight (Ki = 5.8 x 10(-11) M). The inhibition is competitive. These results suggest the possibility of using the invariant chain as a model for the specific inhibition of cruzipain in vivo, i.e. as a potential drug to combat Chagas' disease.
Bevec
T
T
Department of Biochemistry and Molecular Biology, J. Stefan Institute, Ljubljana, Slovenia.
Stoka
V
V
Pungercic
G
G
Cazzulo
J J
JJ
Turk
V
V
D017398:Alternative Splicing; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000494:pharmacology*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000494:pharmacology*; D007700:Kinetics; D010446:Peptide Fragments / Q000494:pharmacology; D015800:Protozoan Proteins; D014349:Trypanosoma cruzi / Q000201:enzymology*
D000944:Antigens, Differentiation, B-Lymphocyte; D015853:Cysteine Proteinase Inhibitors; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D015800:Protozoan Proteins; C045084:invariant chain; D003546:Cysteine Endopeptidases; C063214:cruzipain