VIRAL CYSTEINE PROTEASES ARE HOMOLOGOUS TO THE TRYPSIN-LIKE FAMILY OF SERINE PROTEASES - STRUCTURAL AND FUNCTIONAL IMPLICATIONS
VIRAL CYSTEINE PROTEASES ARE HOMOLOGOUS TO THE TRYPSIN-LIKE FAMILY OF SERINE PROTEASES - STRUCTURAL AND FUNCTIONAL IMPLICATIONS
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DOI：
10.1073/pnas.85.21.7872
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发表时间：
1988-11-01
影响因子：
11.1
通讯作者：
FLETTERICK, RJ
中科院分区：
文献类型：
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作者：
BAZAN, JF;FLETTERICK, RJ
由动物小核糖核酸病毒和植物共病毒和多病毒编码的蛋白酶形成了一组相关的半胱氨酸活性中心酶，这些酶对病毒成熟至关重要。我们发现这些蛋白与胰蛋白酶样丝氨酸蛋白酶家族同源。在我们的模型中，胰蛋白酶催化三联体的活性位点亲核试剂Ser-195在这些病毒蛋白酶中变成了Cys残基。另外两个三联体残基His-57和Asp-102在所有的病毒蛋白酶序列中都是绝对保守的。比对序列的二级结构分析表明了双胞胎。β的组成链的位置。桶状胰蛋白酶在病毒蛋白酶中折叠。出乎意料的是，病毒半胱氨酸蛋白酶的2a和3c亚类分别与胰蛋白酶样丝氨酸蛋白酶的小亚类和大结构亚类同源。这种分类允许从病毒序列到相关三级结构的残基分子作图；我们精确地确定氨基酸是特异性的强决定因素为小和大的病毒半胱氨酸蛋白酶。
Proteases that are encoded by animal picornaviruses and plant como- and potyviruses form a related group of cysteine-active-center enzymes that are essential for virus maturation. We show that these proteins are homologous to the family of trypsin-like serine proteases. In our model, the active-site nucleophile of the trypsin catalytic triad, Ser-195, is changed to a Cys residue in these viral proteases. The other two residues of the triad, His-57 and Asp-102, are otherwise absolutely conserved in all the viral protease sequences. Secondary structure analysis of aligned sequences suggests the location of the component strands of the twin .beta.-barrel trypsin fold in the viral proteases. Unexpectedly, the 2a and 3c subclasses of viral cysteine proteases are, respectively, homologous to the small and large structural subclasses of trypsin-like serine proteases. This classification allows the molecular mapping of residues from viral sequences onto related tertiary structures; we precisely identify amino acids that are strong determinants of specificity for both small and large viral cysteine proteases.