对抗烷基化诱变的自杀性甲基转移酶的活性位点及完整序列。
Active site and complete sequence of the suicidal methyltransferase that counters alkylation mutagenesis.
作者信息
Demple B, Sedgwick B, Robins P, Totty N, Waterfield M D, Lindahl T
出版信息
Proc Natl Acad Sci U S A. 1985 May;82(9):2688-92. doi: 10.1073/pnas.82.9.2688.
Abstract
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 cysteine residues. We have determined the DNA sequence of the cloned ada+ gene and its regulatory region. 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 present at the active site of thymidylate synthase, suggesting a common chemical mechanism for activation of the cysteine.
摘要
大肠杆菌中对烷基化诱变和杀伤的诱导抗性（适应性反应）由ada基因控制。Ada蛋白既是该反应的正调控因子，又是一种DNA修复酶，通过将烷基自杀性转移至自身的一个半胱氨酸残基来校正DNA中诱变前的O6-烷基鸟嘌呤。我们已确定克隆的ada⁺基因及其调控区域的DNA序列。数据揭示了ada自身调控的潜在位点。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多肽COOH末端附近，具有不寻常的序列-Pro-Cys-His-，其前面是一个非常疏水的区域。胸苷酸合酶的活性位点也存在这些相同的结构特征，这表明半胱氨酸激活存在共同的化学机制。
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