Structure and mechanism of mRNA cap (guanine-N7) methyltransferase

被引：129

作者：

Fabrega, C

Hausmann, S

Shen, V

Shuman, S

Lima, CD ^{[1
]}

机构：

[1] Cornell Univ, Weill Med Coll, Dept Biochem, Struct Biol Program, New York, NY 10021 USA

[2] Sloan Kettering Inst, Program Mol Biol, New York, NY 10021 USA

[3] Sloan Kettering Inst, Struct Biol Program, New York, NY 10021 USA

来源：

MOLECULAR CELL | 2004年 / 13卷 / 01期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/S1097-2765(03)00522-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A suite of crystal structures is reported for a cellular mRNA cap (guanine-N7) methyltransferase in complex with AdoMet, AdoHcy, and the cap guanylate. Super-position of ligand complexes suggests an in-line mechanism of methyl transfer, albeit without direct contacts between the enzyme and either the N7 atom of guanine (the attacking nucleophile), the methyl carbon of AdoMet, or the sulfur of AdoMet/AdoHcy (the leaving group). The structures indicate that catalysis of cap N7 methylation is accomplished by optimizing proximity and orientation of the substrates, assisted by a favorable electrostatic environment. The enzyme-ligand structures, together with new mutational data, fully account for the biochemical specificity of the cap guanine-N7 methylation reaction, an essential and defining step of eukaryotic mRNA synthesis.

引用

页码：77 / 89

页数：13

共 63 条

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