CYSTEINE PROTEASES OF POSITIVE STRAND RNA VIRUSES AND CHYMOTRYPSIN-LIKE SERINE PROTEASES - A DISTINCT PROTEIN SUPERFAMILY WITH A COMMON STRUCTURAL FOLD
CYSTEINE PROTEASES OF POSITIVE STRAND RNA VIRUSES AND CHYMOTRYPSIN-LIKE SERINE PROTEASES - A DISTINCT PROTEIN SUPERFAMILY WITH A COMMON STRUCTURAL FOLD
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DOI：
10.1016/0014-5793(89)80109-7
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发表时间：
1989-01-30
期刊：
影响因子：
3.5
通讯作者：
KOONIN, EV
中科院分区：
文献类型：
--
作者：
GORBALENYA, AE;DONCHENKO, AP;KOONIN, EV
基于序列比较和二级结构预测，提供了胰凝乳蛋白酶样丝氨酸蛋白酶、正链RNA病毒的半胱氨酸蛋白酶（小核糖核酸病毒的3C蛋白酶和como-、nepo-和potyviruses的相关酶）和sobemovirus的推定丝氨酸蛋白酶之间的结构和进化关系的证据。这些观察导致重新鉴定病毒蛋白酶的主要催化残基。与位于 3C 蛋白酶 C 端部分的一对 Cys 和 His 不同，已鉴定出保守的 His、Asp(Glu) 和 Cys(Ser) 三联体，前两个残基位于 N 端，Cys 位于 C 端 β-桶结构域。这些残基被认为形成了类似于胰凝乳蛋白酶样蛋白酶的催化三联体所形成的电荷转移系统。基于与胰凝乳蛋白酶样蛋白酶的结构相似性，先前涉及催化作用的组氨酸残基与两个部分保守的甘氨酸残基一起，预计将构成 3C 蛋白酶底物结合口袋的一部分。位于催化 Cys 之前的环中的部分保守的 ThrLys/Arg 二肽被认为赋予 3C 对 Glx/Gly(Ser) 位点的初级切割特异性。这些观察结果提供了根据定义属于不同类别的蛋白酶之间相关性的第一个例子。
Evidence is presented, based on sequence comparison and secondary structure prediction, of structural and evolutionary relationship between chymotrypsin-like serine proteases, cysteine proteases of positive strand RNA viruses (3C proteases of picornaviruses and related enzymes of como-, nepo- and potyviruses) and putative serine protease of a sobemovirus. These observations lead to re-identification of principal catalytic residues of viral proteases. Instead of the pair of Cys and His, both located in the C-terminal part of 3C proteases, a triad of conserved His, Asp(Glu) and Cys(Ser) has been identified, the first two residues resident in the N-terminal, and Cys in the C-terminal β-barrel domain. These residues are suggested to form a charge-transfer system similar to that formed by the catalytic triad of chymotrypsin-like proteases. Based on the structural analogy with chymotrypsin-like proteases, the His residue previously implicated in catalysis, together with two partially conserved Gly residues, is predicted to constitute part of the substrate-binding pocket of 3C proteases. A partially conserved ThrLys/Arg dipeptide located in the loop preceding the catalytic Cys is suggested to confer the primary cleavage specificity of 3C toward Glx/Gly(Ser) sites. These observations provide the first example of relatedness between proteases belonging, by definition, to different classes.