tRNAHis guanylyltransferase (THG1), a unique 3′-5′ nucleotidyl transferase, shares unexpected structural homology with canonical 5′-3′ DNA polymerases
tRNAHis guanylyltransferase (THG1), a unique 3′-5′ nucleotidyl transferase, shares unexpected structural homology with canonical 5′-3′ DNA polymerases
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DOI：
10.1073/pnas.1010436107
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发表时间：
2010-11-23
影响因子：
11.1
通讯作者：
Doublie, Sylvie
中科院分区：
文献类型：
--
作者：
Hyde, Samantha J.;Eckenroth, Brian E.;Doublie, Sylvie
所有已知的DNA和RNA聚合酶都以5'到3'方向催化磷酸二酯键的形成，这表明这种性质是维持和分散遗传信息的基本特征。tRNA（His）鸟苷酰转移酶（Thg 1）是一个独特的酶家族的成员，其成员催化生物学中前所未有的反应：核苷酸与核酸底物的3 '-5'加成。本文报道的人THG 1（hTHG 1）的2.3埃晶体结构表明，尽管缺乏序列相似性，hTHG 1与典型的5 '-3' DNA聚合酶和腺苷酸/鸟苷酸环化酶（已知使用双金属离子机制进行催化的两种酶家族）具有意想不到的结构同源性。相同的结构架构催化5 '-3'和3 '-5'反应的能力提出了关于核苷酸聚合酶进化过程中5 '-3'机制选择的重要问题。
All known DNA and RNA polymerases catalyze the formation of phosphodiester bonds in a 5' to 3'direction, suggesting this property is a fundamental feature of maintaining and dispersing genetic information. The tRNA(His) guanylyltransferase (Thg1) is a member of a unique enzyme family whose members catalyze an unprecedented reaction in biology: 3'-5' addition of nucleotides to nucleic acid substrates. The 2.3-angstrom crystal structure of human THG1 (hTHG1) reported here shows that, despite the lack of sequence similarity, hTHG1 shares unexpected structural homology with canonical 5'-3' DNA polymerases and adenylyl/guanylyl cyclases, two enzyme families known to use a two-metal-ion mechanism for catalysis. The ability of the same structural architecture to catalyze both 5'-3' and 3'-5' reactions raises important questions concerning selection of the 5'-3' mechanism during the evolution of nucleotide polymerases.