RATIONAL APPROACHES TO THE DESIGN OF ANTIVIRAL AGENTS BASED ON S-ADENOSYL-L-HOMOCYSTEINE HYDROLASE AS A MOLECULAR TARGET
RATIONAL APPROACHES TO THE DESIGN OF ANTIVIRAL AGENTS BASED ON S-ADENOSYL-L-HOMOCYSTEINE HYDROLASE AS A MOLECULAR TARGET
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DOI：
10.1016/0166-3542(92)90083-h
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发表时间：
1992-09-01
影响因子：
7.6
通讯作者：
BORCHARDT, RT
中科院分区：
文献类型：
--
作者：
LIU, S;WOLFE, MS;BORCHARDT, RT
S-腺苷-L-蛋氨酸(ADO-Met)依赖的反甲基化在调节各种生化和生理过程中起着重要作用(Borchardt，1980；Borchardt et al.，1986)。我们实验室感兴趣的一个特殊的生化过程是在病毒mRNA的Y末端形成“有帽的甲基化结构”(Keller和Borchardt，1986)。大多数病毒mRNAs都含有这种新的5‘末端封端结构，这是病毒mRNA翻译和病毒在真核细胞中复制所必需的(Banerjee，1980)。所有的封端甲基化结构由N-7-甲基鸟苷残基组成，通过三磷酸连接在5‘-羟基处与mRNA链的Y-端相连。大多数被封顶的甲基化结构在倒数第二个核苷酸的2‘-羟基上也含有甲基(图3)。洛杉矶)。信使核糖核酸5‘末端的甲基化是由依赖于Adobe Met的鸟苷7-N-甲基转移酶和核苷2’-甲基转移酶催化的，这两种酶都是细胞和病毒编码的酶(图4)。Lb)。
S-Adenosyl-L-methionine (AdoMet)-dependent transmethylations play an important role in regulating various biochemical and physiological processes (Borchardt, 1980; Borchardt et al., 1986). A specific biochemical process of interest to our laboratory is the formation of the'capped methylated structure'at the Y-terminus of viral mRNA (Keller and Borchardt, 1986). Most viral mRNAs have been found to contain this novel 5'-terminal capped structure, which is essential for viral mRNA translation and thus viral replication in eukaryotic cells (Banerjee, 1980). All capped methylated structures consist of a N-7-methyl guanosine residue linked at the 5'-hydroxyl group to the Y-end of the mRNA strand by a triphosphate linkage. Most capped methylated structures also contain a methyl group on the 2'-hydroxyl group of the penultimate nucleotide (Fig. la). Methylations at the 5'-terminus of mRNA are catalyzed by AdoMet-dependent guanosine 7-N-methyltransferase and nucleoside 2'-methyltransferase, which are both cellular and viral encoded enzymes (Fig. lb).