Crystal structure of a replicative DNA polymerase bound to the oxidized guanine lesion guanidinohydantoin.
Crystal structure of a replicative DNA polymerase bound to the oxidized guanine lesion guanidinohydantoin.
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DOI：
10.1021/bi902195p
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发表时间：
2010-03-23
期刊：
影响因子：
2.9
通讯作者：
Doublie, Sylvie
中科院分区：
文献类型：
--
作者：
Aller, Pierre;Ye, Yu;Wallace, Susan S.;Burrows, Cynthia J.;Doublie, Sylvie
鸟嘌呤的氧化产生最常见的DNA损伤之一，8-氧-7,8-二氢鸟嘌呤（8-oxoG）。8-oxoG的进一步氧化可以在双链DNA中产生胍酰肼（Gh）或在核苷和ssDNA中产生螺酰亚胺二酰肼（Sp）。虽然Gh对复制性DNA聚合酶（如RB69 DNA聚合酶）具有很强的阻滞作用，但这种损害也是致突变性的：DNA聚合酶通过优先结合嘌呤而忽略Gh，并优先结合腺嘌呤，从而导致G•C→T•a或G•C→C•G转化。复制性RB69 DNA聚合酶与含有Gh的DNA复合物的2.15 Å晶体结构表明Gh是外螺旋的，并向主槽旋转。在这种构象中，Gh不再处于将进入的核苷酸结合的模板碱基的位置。这项工作也构成了Gh的第一个晶体结构，它在晶体不对称单元中存在的两个聚合酶/DNA复合物中稳定在R构型中。与8-oxoG相反，Gh在DNA双链中呈高syn构象，因此呈现与胸腺嘧啶相同的氢键供体和受体模式，这解释了DNA聚合酶在旁路发生时倾向于结合与Gh相反的嘌呤。
The oxidation of guanine generates one of the most common DNA lesions, 8-oxo-7,8-dihydroguanine (8-oxoG). The further oxidation of 8-oxoG can produce either guanidinohydantoin (Gh) in duplex DNA or spiroiminodihydantoin (Sp) in nucleosides and ssDNA. Although Gh can be a strong block for replicative DNA polymerases such as RB69 DNA polymerase this lesion is also mutagenic: DNA polymerases bypass Gh by preferentially incorporating a purine with a slight preference for adenine, which results in G•C → T•A or G•C → C•G transversions. The 2.15 Å crystal structure of the replicative RB69 DNA polymerase in complex with DNA containing Gh reveals that Gh is extrahelical and rotated toward the major groove. In this conformation Gh is no longer in position to serve as a templating base for the incorporation of an incoming nucleotide. This work also constitutes the first crystallographic structure of Gh, which is stabilized in the R configuration in the two polymerase/DNA complexes present in the crystal asymmetric unit. In contrast to 8-oxoG, Gh is found in a high syn conformation in the DNA duplex and therefore presents the same hydrogen bond donor and acceptor pattern as thymine, which explains the propensity of DNA polymerases to incorporate a purine opposite Gh when bypass occurs.
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影响因子：
64.5
作者：
Franklin, MC;Wang, JM;Steitz, TA
通讯作者：
Steitz, TA
影响因子：
4.1
作者：
Hailer, MK;Slade, PG;Sugden, KD
通讯作者：
Sugden, KD
影响因子：
2.9
作者：
Krishnamurthy, Nirmala;Zhao, Xiaobei;David, Sheila S.
通讯作者：
David, Sheila S.
DOI：
10.1107/s0907444998003254
发表时间：
1998-09-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Brunger, AT;Adams, PD;Warren, GL
通讯作者：
Warren, GL
影响因子：
2.9
作者：
Delaney, Sarah;Neeley, William L.;Essigmann, John M.
通讯作者：
Essigmann, John M.