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首页> 外文期刊>Journal of Molecular Biology >Crystal structure of Stefin A in complex with cathepsin H: N-terminal residues of inhibitors can adapt to the active sites of endo- and exopeptidases.
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Crystal structure of Stefin A in complex with cathepsin H: N-terminal residues of inhibitors can adapt to the active sites of endo- and exopeptidases.

机译：Stefin A与组织蛋白酶H的复合物的晶体结构：抑制剂的N末端残基可适应内肽酶和外肽酶的活性位点。

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摘要

Binding of cystatin-type inhibitors to papain-like exopeptidases cannot be explained by the stefin B-papain complex. The crystal structure of human stefin A bound to an aminopeptidase, porcine cathepsin H, has been determined in monoclinic and orthorhombic crystal forms at 2.8A and 2.4A resolutions, respectively. The asymmetric unit of each form contains four complexes. The structures are similar to the stefin B-papain complex, but with a few distinct differences. On binding, the N-terminal residues of stefin A adopt the form of a hook, which pushes away cathepsin H mini-chain residues and distorts the structure of the short four residue insertion (Lys155A-Asp155D) unique to cathepsin H. Comparison with the structure of isolated cathepsin H shows that the rims of the cathepsin H structure are slightly displaced (up to 1A) from their position in the free enzyme. Furthermore, comparison with the stefin B-papain complex showed that molecules of stefin A bind about 0.8A deeper into the active site cleft ofcathepsin H than stefin B into papain. The approach of stefin A to cathepsin H induces structural changes along the interaction surface of both molecules, whereas no such changes were observed in the stefin B-papain complex. Carboxymethylation of papain seems to have prevented the formation of the genuine binding geometry between a papain-like enzyme and a cystatin-type inhibitor as we observe it in the structure presented here.
机译：胱抑素类型的抑制剂与木瓜蛋白酶样肽酶的结合不能用Stefin B-木瓜蛋白酶复合物来解释。已分别以2.8A和2.4A的分辨率确定单斜晶和正交晶形式的人Stefin A与氨基肽酶（猪组织蛋白酶H）结合的晶体结构。每种形式的不对称单元包含四个复合物。其结构与Stefin B-木瓜蛋白酶复合物相似，但有一些明显的不同。结合时，Stefin A的N末端残基采用钩子的形式，将组织蛋白酶H的微链残基推开，并使组织蛋白酶H特有的短的四个残基插入（Lys155A-Asp155D）的结构变形。分离的组织蛋白酶H的结构表明，组织蛋白酶H结构的边缘从其在游离酶中的位置略有移位（最大1A）。此外，与Stefin B-木瓜蛋白酶复合物的比较表明，与Stefin B进入木瓜蛋白酶相比，Stefin A分子在蛋白酶C的活性位点深处结合的深度约为0.8A。 Stefin A对组织蛋白酶H的方法沿两个分子的相互作用表面诱导结构变化，而在Stefin B-木瓜蛋白酶复合物中未观察到这种变化。木瓜蛋白酶的羧甲基化作用似乎阻止了木瓜蛋白酶样酶和半胱氨酸蛋白酶抑制剂抑制剂之间真正的结合几何结构的形成，正如我们在此处介绍的结构中观察到的那样。

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