DNA-N-glycosylases process novel O-glycosidic sites in DNA.
DNA-N-glycosylases process novel O-glycosidic sites in DNA.
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DOI：
10.1021/bi400218j
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发表时间：
2013-06-11
期刊：
影响因子：
2.9
通讯作者：
O'Brien PJ
中科院分区：
文献类型：
--
作者：
Admiraal SJ;O'Brien PJ
在水解 DNA 脱氧核糖基部分的受损碱基和 C1' 之间的 N-糖基键后，人烷基腺嘌呤 DNA 糖基化酶 (AAG) 和大肠杆菌 3-甲基腺嘌呤 DNA 糖基化酶 II (AlkA) 与其脱碱基 DNA 产物紧密结合，从而潜在地保护这些活性物质。在这里，我们证明 AAG 和 AlkA 都能催化结合的脱碱基 DNA 和小伯醇之间的反应，形成新型 DNA-O-糖苷。合成反应是可逆的，因为在没有酒精的情况下与 AAG 或 AlkA 一起孵育时，DNA-O-糖苷会转化回脱碱基 DNA。因此，除了 N-糖基键外，AAG 和 AlkA 还能够水解 O-糖苷键。新发现的这两种酶的 DNA-O-糖苷酶活性与其已知的 DNA-N-糖苷酶活性相比毫不逊色：AAG 从 DNA 中去除甲醇和 1,N6-乙烯腺嘌呤 (εA)，单周转速率常数比相应的未催化速率高 2.9×105 倍，而 AlkA 从 DNA 中去除甲醇的速率增强 3.7×107，高出 300 倍比其从 DNA 中去除 εA 的速率增强。尽管 DNA-O-糖苷酶反应的生物学意义尚不清楚，但新的 DNA 修复途径的进化可能会受到催化混杂酶的帮助，例如这两种不相关的 DNA 糖基化酶。
After hydrolyzing the N-glycosyl bond between a damaged base and C1' of a deoxyribosyl moiety of DNA, human alkyladenine DNA glycosylase (AAG) and E. coli 3-methyladenine DNA glycosylase II (AlkA) bind tightly to their abasic DNA products, potentially protecting these reactive species. Here we show that both AAG and AlkA catalyze reactions between bound abasic DNA and small, primary alcohols to form novel DNA-O-glycosides. The synthesis reactions are reversible, as the DNA-O-glycosides are converted back into abasic DNA when incubated with AAG or AlkA in the absence of alcohol. AAG and AlkA are therefore able to hydrolyze O-glycosidic bonds in addition to N-glycosyl bonds. The newly discovered DNA-O-glycosidase activities of both enzymes compare favorably with their known DNA-N-glycosylase activities: AAG removes both methanol and 1,N6-ethenoadenine (εA) from DNA with single turnover rate constants that are 2.9×105-fold greater than the corresponding uncatalyzed rates, whereas the rate enhancement of 3.7×107 for removal of methanol from DNA by AlkA is 300-fold greater than its rate enhancement for removal of εA from DNA. Although the biological significance of the DNA-O-glycosidase reactions is not known, the evolution of new DNA repair pathways may be aided by enzymes that practice catalytic promiscuity, such as these two unrelated DNA glycosylases.
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影响因子：
4.8
作者：
Abner, CW;Lau, AY;Bloom, LB
通讯作者：
Bloom, LB
影响因子：
4.8
作者：
O'Brien, PJ;Ellenberger, T
通讯作者：
Ellenberger, T
DOI：
10.1016/0165-1218(93)90092-r
发表时间：
1993-05-01
期刊：
MUTATION RESEARCH
影响因子：
--
作者：
EVANS, J;MACCABEE, M;WALLACE, S
通讯作者：
WALLACE, S
DOI：
10.1107/s0907444903011144
发表时间：
2003-08-01
影响因子：
2.2
作者：
Leiros, I;Moe, E;Willassen, NP
通讯作者：
Willassen, NP
影响因子：
15
作者：
Johnson, Kevin M.;Price, Nathan E.;Wang, Jin;Fekry, Mostafa I.;Dutta, Sanjay;Seiner, Derrick R.;Wang, Yinsheng;Gates, Kent S.
通讯作者：
Gates, Kent S.