Bevec T, Stoka V, Pungercic G, Cazzulo J J, Turk V
Department of Biochemistry and Molecular Biology, J. Stefan Institute, Ljubljana, Slovenia.
FEBS Lett. 1997 Jan 20;401(2-3):259-61. doi: 10.1016/s0014-5793(96)01443-3.
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.
与主要组织相容性复合体（MHC）II类分子相关的恒定链（Ii）的p41形式衍生的肽片段已被证明可抑制哺乳动物溶酶体半胱氨酸蛋白酶组织蛋白酶L，并且是一种新型的半胱氨酸蛋白酶抑制剂，不同于胱抑素。在此我们报告，同一片段也能结合并抑制克氏锥虫蛋白酶，即原生动物寄生虫克氏锥虫的组织蛋白酶L样酶。Ii片段与克氏锥虫蛋白酶的结合迅速（结合速率常数k(ass)=2.4×10(7) M(-1) s(-1)）且紧密（抑制常数Ki = 5.8×10(-11) M）。这种抑制作用具有竞争性。这些结果表明，有可能将恒定链用作体内特异性抑制克氏锥虫蛋白酶的模型，即作为对抗恰加斯病的潜在药物。
