Shuman S, Schwer B
Molecular Biology Program, Sloan-Kettering Institute, New York, New York 10021, USA.
Mol Microbiol. 1995 Aug;17(3):405-10. doi: 10.1111/j.1365-2958.1995.mmi_17030405.x.
mRNA capping entails GMP transfer from GTP to a 5' diphosphate RNA end to form the structure G(5')ppp(5')N. A similar reaction involving AMP transfer to the 5' monophosphate end of DNA or RNA occurs during strand joining by polynucleotide ligases. In both cases, nucleotidyl transfer occurs through a covalent lysyl-NMP intermediate. Sequence conservation among capping enzymes and ATP-dependent ligases in the vicinity of the active site lysine (KxDG) and at five other co-linear motifs suggests a common structural basis for covalent catalysis. Mutational studies support this view. We propose that the cellular and DNA virus capping enzymes and ATP-dependent ligases constitute a protein superfamily evolved from a common ancestral enzyme. Within this superfamily, the cellular capping enzymes display more extensive similarity to the ligases than they do to the poxvirus capping enzymes. Recent studies suggest that eukaryotic RNA viruses have evolved alternative pathways of cap metabolism catalysed by structurally unrelated enzymes that nonetheless employ a phosphoramidate intermediate. Comparative analysis of these enzymes, particularly at the structural level, should illuminate the shared reaction mechanism while clarifying the basis for nucleotide specificity and end recognition. The capping enzymes merit close attention as potential targets for antiviral therapy.
信使核糖核酸（mRNA）加帽涉及将鸟苷一磷酸（GMP）从鸟苷三磷酸（GTP）转移至5'二磷酸核糖核酸末端，以形成结构G(5')ppp(5')N。在多核苷酸连接酶进行链连接过程中，会发生类似的反应，即将腺苷一磷酸（AMP）转移至DNA或RNA的5'单磷酸末端。在这两种情况下，核苷酸转移均通过共价赖氨酰-NMP中间体进行。加帽酶与ATP依赖性连接酶在活性位点赖氨酸（KxDG）附近以及其他五个共线基序处的序列保守性表明，共价催化具有共同的结构基础。突变研究支持这一观点。我们提出，细胞和DNA病毒加帽酶以及ATP依赖性连接酶构成了一个从共同祖先酶进化而来的蛋白质超家族。在这个超家族中，细胞加帽酶与连接酶的相似性比与痘病毒加帽酶的相似性更为广泛。最近的研究表明，真核RNA病毒已经进化出由结构不相关的酶催化的帽代谢替代途径，这些酶仍然使用氨基磷酸中间体。对这些酶进行比较分析，尤其是在结构层面，应能阐明共同的反应机制，同时明确核苷酸特异性和末端识别的基础。加帽酶作为抗病毒治疗的潜在靶点值得密切关注。
