Zinov'ev V V, Evdokimov A A, Hattman S, Malygin E G
Mol Biol (Mosk). 2004 Sep-Oct;38(5):869-85.
The review reflects results of studies on the molecular mechanism of phage T4 Dam DNA-methyltransferase action. The enzyme (T4Dam) catalyzes methyl group transfer from S-adenosyl-l-methionine (AdoMet) to N6-adenine position in the palindromic recognition sequence GATC (EC 2.1.1.72). The enzyme subunit structure, substrate-binding and kinetic parameters for a wide range of native and modified oligonucleotide duplexes, as well as steady-state reaction kinetic scheme, included T4Dam isomerization to catalytically active form, are considered. The found mechanisms of DNA induced T4Dam dimerization, target base flipping, enzyme reorientation in an asymmetrically modified recognition sequence, effector action of reaction substrates and processive methylation of DNA substrates, containing more than one specific site, are discussed. The results obtained with T4Dam may be useful for understanding mechanisms of action of other homologous enzymes, most of all for specimens of numerous family of Dam DNA-methyltransferases.
本综述反映了关于噬菌体T4 Dam DNA甲基转移酶作用分子机制的研究结果。该酶（T4Dam）催化甲基从S-腺苷-L-甲硫氨酸（AdoMet）转移至回文识别序列GATC中的N6-腺嘌呤位点（EC 2.1.1.72）。文中考虑了该酶的亚基结构、多种天然和修饰寡核苷酸双链体的底物结合及动力学参数，以及稳态反应动力学方案，其中包括T4Dam异构化为催化活性形式。讨论了所发现的DNA诱导T4Dam二聚化、靶碱基翻转、酶在不对称修饰识别序列中的重新定向、反应底物的效应作用以及含多个特定位点的DNA底物的连续甲基化机制。用T4Dam获得的结果可能有助于理解其他同源酶的作用机制，尤其是对众多Dam DNA甲基转移酶家族的样本。
