ACTIVE-SITE AND COMPLETE SEQUENCE OF THE SUICIDAL METHYLTRANSFERASE THAT COUNTERS ALKYLATION MUTAGENESIS
ACTIVE-SITE AND COMPLETE SEQUENCE OF THE SUICIDAL METHYLTRANSFERASE THAT COUNTERS ALKYLATION MUTAGENESIS
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DOI：
10.1073/pnas.82.9.2688
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发表时间：
1985-01-01
影响因子：
11.1
通讯作者：
LINDAHL, T
中科院分区：
文献类型：
--
作者：
DEMPLE, B;SEDGWICK, B;LINDAHL, T
大肠杆菌对烷基化诱变和杀灭的诱导抗性（适应性反应）由 ada 基因控制。 Ada 蛋白既充当反应的正向调节剂，又充当 DNA 修复酶，通过将烷基自杀性转移至其自身的 Cys 残基之一来纠正 DNA 中的诱变前 O6-烷基鸟嘌呤。确定了克隆的ada+基因的DNA序列及其调控区。数据揭示了 ada 自动调节的潜在位点。氨基酸序列测定表明，O6-甲基鸟嘌呤-DNA甲基转移酶的活性中心位于靠近多肽COOH末端，并具有不寻常的序列-Pro-Cys-His，前面是一个非常疏水的区域。这些相同的结构特征出现在胸苷酸合酶的活性位点，表明半胱氨酸激活的常见化学机制。
The inducible resistance to alkylation mutagenesis and killing in Escherichia coli (the adaptive response) is controlled by the ada gene. The Ada protein acts both as a positive regulator of the response and as a DNA repair enzyme, correcting premutagenic O6-alkylguanine in DNA by suicidal transfer of the alkyl group to one of its own Cys residues. The DNA sequence of the cloned ada+ gene and its regulatory region were determined. The data reveal potential sites of ada autoregulation. Amino acid sequence determinations show that the active center for the O6-methylguanine-DNA methyltransferase is located close to the polypeptide COOH terminus and has the unusual sequence -Pro-Cys-His, preceded by a very hydrophobic region. These same structural features are presented at the active site of thymidylate synthase, suggesting a common chemical mechanism for activation of the Cys.