Inhibition of cruzipain, the major cysteine proteinase of the protozoan parasite, Trypanosoma cruzi, by proteinase inhibitors of the cystatin superfamily.
Cruzipain, the major cysteine proteinase from Trypanosoma cruzi epimastigotes, purified to a sequentially pure form, exists in multiple forms with pI values between 3.7 and 5.1, and an apparent molecular mass of 41 kDa. The enzyme is stable between pH 4.5-9.5. Cruzipain was found to be rapidly and tightly inhibited by various protein inhibitors of the cystatin superfamily (kass = 1.7-79 x 10(6) M-1s-1, Kd = 1.4-72 pM). These results suggest a possible defensive role for the host's cystatins after parasite infection, and may be of use for the design of new therapeutic drugs.
Stoka
V
V
Department of Biochemistry and Molecular Biology, J. Stefan Institute, Ljubljana, Slovenia.
Nycander
M
M
Lenarcic
B
B
Labriola
C
C
Cazzulo
J J
JJ
Björk
I
I
Turk
V
V
D000818:Animals; D002645:Chickens; D055312:Cystatin A; D015891:Cystatins / Q000494:pharmacology*; D003546:Cysteine Endopeptidases / Q000302:isolation & purification / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007525:Isoelectric Focusing; D007700:Kinetics; D008970:Molecular Weight; D015800:Protozoan Proteins; D011994:Recombinant Proteins / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000201:enzymology*
D055312:Cystatin A; D015891:Cystatins; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C026407:CSTA protein, human; D003546:Cysteine Endopeptidases; C063214:cruzipain