Distortion of the active site of chymotrypsin complexed with a serpin.
Distortion of the active site of chymotrypsin complexed with a serpin.
复制标题
胰凝乳蛋白酶与丝氨酸蛋白酶抑制剂复合的活性位点变形。
DOI：
10.1021/bi960233w
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Rubin,H
中科院分区：
文献类型：
--
作者：
Plotnick,MI;Mayne,L;Schechter,NM;Rubin,H
对于丝氨酸蛋白酶抑制剂家族的丝氨酸蛋白酶抑制剂如何抑制它们的靶酶还没有完全的了解。结构和生物化学研究表明，丝氨酸蛋白酶抑制剂利用的机制，是从大多数小蛋白质蛋白酶抑制剂提出的标准抑制机制不同。质子核磁共振光谱在本研究中使用，以证明与丝氨酸蛋白酶抑制剂的复合物的酶的催化三联体的原子环境相比，未复合的酶和酶的复合物与标准的机制抑制剂的根本差异。这项工作表明，胰凝乳蛋白酶的活性位点被扭曲时，复杂的丝氨酸蛋白酶抑制剂，并使成立的抑制机制，其中丝氨酸蛋白酶抑制剂诱导的构象变化的酶，显着降低或完全废除的催化活性的蛋白酶。
There is no complete understanding of how serine protease inhibitors of the serpin family inhibit their target enzymes. Structural and biochemical studies have suggested that serpins utilize a mechanism that is distinct from the standard mechanism of inhibition proposed for most small protein protease inhibitors. Proton nuclear magnetic resonance spectroscopy was used in the present study to demonstrate a fundamental difference in the atomic environment of the catalytic triad of enzyme in complex with serpins when compared to uncomplexed enzyme and enzyme in complex with standard mechanism inhibitors. This work demonstrates that the active site of chymotrypsin is distorted when complexed to a serpin and makes tenable a mechanism of inhibition in which the serpin induces a conformational change in the enzyme that dramatically reduces or completely abrogates the catalytic activity of the protease.