Inhibition of cruzipain, the major cysteine proteinase of the protozoan parasite, Trypanosoma cruzi, by proteinase inhibitors of the cystatin superfamily

• Published in: FEBS letters 1995-08, Vol.370 (1), p.101-104
• Main Authors: Stoka, Veronika, Nycander, Maria, Lenarčič, Brigita, Labriola, Carlos, Cazzulo, Juan José, Björk, Ingemar, Turk, Vito
• Format: Article
• Language: English
• Subjects: 1-[L-N-(trans-epoxysuccinyl)leucyl]amino-4-guanidino butane; 4-methyl-7-coumarylamide; AMC; Animals; benzyloxycarbonyl; Chickens; Cruzipain; Cystatin; Cystatin A; Cystatins - pharmacology; Cysteine Endopeptidases - isolation & purification; Cysteine Endopeptidases - metabolism; Cysteine proteinase; E-64; EDTA; Electrophoresis, Polyacrylamide Gel; Ep-475; ethylenediaminetetraacetic acid; fast protein liquid chromatography; FPLC; Humans; Inhibition; Isoelectric Focusing; isoelectric point; Kinetics; L-trans-epoxysuccinylleucylamido-(3-guanidino)butane; Molecular Weight; PAGE; polyacrylamide gel electrophoresis; Protozoan Proteins; Recombinant Proteins - pharmacology; relative molecular weight; SDS; sodium dodecyl sulphate; Trypanosoma cruzi; Trypanosoma cruzi - enzymology
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(95)00798-E

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 ( k ass = 1.7–79 × 10 6M −1s −1, K d = 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.