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首页> 外文期刊>Biochemistry >The novel bovine serpin endopin 2C demonstrates selective inhibition of the cysteine protease cathepsin L compared to the serine protease elastase, in cross-class inhibition
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The novel bovine serpin endopin 2C demonstrates selective inhibition of the cysteine protease cathepsin L compared to the serine protease elastase, in cross-class inhibition

机译：与丝氨酸蛋白酶弹性蛋白酶相比，新型牛丝氨酸蛋白酶抑制剂endopin 2C表现出对半胱氨酸蛋白酶组织蛋白酶L的选择性抑制作用

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摘要

Molecular cloning revealed the unique serpin endopin 2C that demonstrates selective inhibition of cathepsin L compared to papain or elastase. Endopin 2C, thus, functions as a serpin with the property of cross-class inhibition. Endopin 2C possesses homology in primary sequence to endopin 2A and other isoforms of endopins related to (alpha(1)-antichymotrypsin, yet endopin 2C differs in its target protease specificity. Recombinant endopin 2C showed effective inhibition of cathepsin L with a stoichiometry of inhibition (SI) of 1/1 (molar ratio of inhibitor/protease), with the second-order rate constant, k(ass), of 7.2 x 10(5) M-1 s(-1). Less effective endopin 2C inhibition of papain and elastase occurred with kass association rate constants of approximately I x 101 M-1 s-1 with high SI values. Endopin 2C formed SDS-stable complexes with cathepsin L, papain, and elastase that are typical of serpins. These results are among the first to demonstrate stable serpin complexes with target cysteine proteases. Interactions of endopin 2C with cathepsin L and elastase were indicated by protease cleavage of the RSL region between P1-P1' residues of Thr-Ser. The hydrophobic Phe residue in the P2 position of the RSL region is consistent with the specificity of cathepsin L for hydrophobic residues in the P2 position of its substrate cleavage site. The NH2-terminal signal sequence of endopin 2C, like that of cathepsin L, predicts their colocalization to subcellular organelles. These findings demonstrate endopin 2C as a novel serpin that possesses cross-class inhibition with selectivity for inhibition of cathepsin L.
机译：分子克隆揭示了独特的丝氨酸蛋白酶抑制剂内切蛋白2C，与木瓜蛋白酶或弹性蛋白酶相比，该蛋白证明了对组织蛋白酶L的选择性抑制。因此，内切蛋白2C充当具有交叉类抑制特性的丝氨酸蛋白酶抑制剂。内啡肽2C与内啡肽2A和其他与（alpha（1）-antichymotrypsin相关的内啡肽同工型在一级序列上具有同源性，但内啡肽2C的靶蛋白酶特异性不同。重组内啡肽2C显示出对组织蛋白酶L的有效抑制和化学计量比的抑制作用（ SI）为1/1（抑制剂/蛋白酶的摩尔比），其二级速率常数k（ass）为7.2 x 10（5）M-1 s（-1）。木瓜蛋白酶和弹性蛋白酶的kass缔合速率常数约为I x 101 M-1 s-1，SI值较高;内膜蛋白2C与组织蛋白酶L，木瓜蛋白酶和弹性蛋白酶形成了SDS稳定的复合物，是丝氨酸蛋白酶抑制剂的典型代表。第一个展示了稳定的丝氨酸蛋白酶抑制剂与目标半胱氨酸蛋白酶的复合物，内蛋白酶2C与组织蛋白酶L和弹性蛋白酶的相互作用通过蛋白酶切割Thr-Ser的P1-P1'残基之间的RSL区来表明。 RSL区域是与组织蛋白酶L对其底物裂解位点P2位置的疏水残基的特异性一致。像组织蛋白酶L一样，endopin 2C的NH2末端信号序列预测它们在亚细胞器中的共定位。这些发现表明，endopin 2C是一种新型的丝氨酸蛋白酶抑制剂，具有交叉类抑制作用，对组织蛋白酶L具有选择性抑制作用。

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