A fragment of the major histocompatibility complex class II – associated p41 invariant chain inhibits cruzipain, the major cysteine proteinase from Trypanosoma cruzi

FEBS Letters

Pungerčič, Galina¹  Bevec, Tadeja¹  Cazzulo, Juan José²  Turk, Vito¹  Stoka, Veronika¹ 

[1] Department of Biochemistry and Molecular Biology, J. Stefan Institute, Jamova 39, 1111 Ljubljana, Slovenia;Instituto de Investigaciones Bioquı́micas ‘Luis F. Leloir’, Fundación Campomar, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Antonio Machado 151, 1405 Buenos Aires, Argentina

关键词: Cruzipain;    Trypanosoma cruzi;    Invariant chain;    p41;    Cysteine proteinase inhibitor;    Inhibition;    C-;    carboxyl-;    DTE;    dithioerythritol;    E-64;    l-3-carboxy-trans-2;    3-epoxypropylleucylamido(4-guanidino)butane;    Ep-475;    l-3-carboxy-trans-2;    3-epoxypropylleucylamido(3-guanidino)butane;    Ii;    invariant chain;    -MCA;    -4-methyl-7-coumarylamide;    MHC;    major histocompatibility complex;    Z-;    benzyloxycarbonyl-;   

DOI  :  10.1016/S0014-5793(96)01443-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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=2.4×10⁷ M⁻¹ s⁻¹) and tight (K _i=5.8×10⁻¹¹ 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.

【 授权许可】

Unknown