PICORNAVIRAL 3C CYSTEINE PROTEINASES HAVE A FOLD SIMILAR TO CHYMOTRYPSIN-LIKE SERINE PROTEINASES
PICORNAVIRAL 3C CYSTEINE PROTEINASES HAVE A FOLD SIMILAR TO CHYMOTRYPSIN-LIKE SERINE PROTEINASES
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DOI：
10.1038/369072a0
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发表时间：
1994-05-05
期刊：
影响因子：
64.8
通讯作者：
JAMES, MNG
中科院分区：
文献类型：
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作者：
ALLAIRE, M;CHERNAIA, MM;JAMES, MNG
小核糖核酸病毒家族包括几种病原体，如脊髓灰质炎病毒、鼻病毒（普通感冒的主要原因）、甲型肝炎病毒和口蹄疫病毒。小核糖核酸病毒蛋白通过基因组RNA直接翻译成单个大的多蛋白前体来表达（1，2）。病毒3C酶（半胱氨酸蛋白酶）确保病毒多蛋白水解为成熟蛋白（3-6）。本文报道了甲型肝炎病毒3C蛋白酶（HAV-3C）在2.3埃分辨率下的晶体结构。HAV-3C的整体结构显示类似于丝氨酸蛋白酶的胰凝乳蛋白酶家族的折叠，这与早期的预测一致（7，8）。催化残基包括作为亲核试剂的Cys 172和作为通用碱基的His 44。谷氨酰胺残基的3C切割特异性主要由His 191定义。整体结构表明，分子间（反式）裂解释放3C，并在多聚蛋白中有活性蛋白酶。
THE picornavirus family includes several pathogens such as poliovirus, rhinovirus (the major cause of the common cold), hepatitis A virus and the foot-and-mouth disease virus. Picornaviral proteins are expressed by direct translation of the genomic RNA into a single, large polyprotein precursor(1,2). Proteolysis of the viral polyprotein into the mature proteins is assured by the viral 3C enzymes, which are cysteine proteinases(3-6). Here we report the Xray crystal structure at 2.3 Angstrom resolution of the 3C proteinase from hepatitis A virus (HAV-3C). The overall architecture of HAV-3C reveals a fold resembling that of the chymotrypsin family of serine proteinases, which is consistent with earlier predictions(7,8). Catalytic residues include Cys 172 as nucleophile and His 44 as general base. The 3C cleavage specificity for glutamine residues is defined primarily by His 191. The overall structure suggests that an intermolecular (trans) cleavage releases 3C and that there is an active proteinase in the polyprotein.