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

FEBS Letters

Lenarčič, Brigita²  Björk, Ingemar³  Nycander, Maria³  Cazzulo, Juan José¹  Labriola, Carlos¹  Turk, Vito²  Stoka, Veronika² 

[1] Instituto de Investigaciones Bioquímicas ‘Luis F. Leloir’, Fundación Campomar-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Antonio Machado 151, 1405 Buenos Aires, Argentina;Department of Biochemistry and Molecular Biology, J. Stefan Institute, Jamova 39, 61111 Ljubljana, Slovenia;Department of Veterinary Medical Chemistry, Swedish University of Agricultural Sciences, Uppsala Biomedical Center, Box 575, S-751 23 Uppsala, Sweden

关键词: Trypanosoma cruzi;    Cruzipain;    Cysteine proteinase;    Cystatin;    Inhibition;    Kinetics;    -AMC;    4-methyl-7-coumarylamide;    EDTA;    ethylenediaminetetraacetic acid;    E-64;    1-[L-N-(trans-epoxysuccinyl)leucyl]amino-4-guanidino butane;    Ep-475;    L-trans-epoxysuccinylleucylamido-(3-guanidino)butane;    FPLC;    fast protein liquid chromatography;    Mr;    relative molecular weight;    PAGE;    polyacrylamide gel electrophoresis;    pI;    isoelectric point;    SDS;    sodium dodecyl sulphate;    Z;    benzyloxycarbonyl;   

DOI  :  10.1016/0014-5793(95)00798-E

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 × 10⁶M⁻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.

【 授权许可】

Unknown