Eckenroth Brian E, Fleming Aaron M, Sweasy Joann B, Burrows Cynthia J, Doublié Sylvie
Department of Microbiology and Molecular Genetics, University of Vermont , Stafford Hall, 95 Carrigan Drive, Burlington, Vermont 05405, United States.
Biochemistry. 2014 Apr 8;53(13):2075-7. doi: 10.1021/bi500270e. Epub 2014 Mar 26.
The first high-resolution crystal structure of spiroiminodihydantoin (dSp1) was obtained in the context of the DNA polymerase β active site and reveals two areas of significance. First, the structure verifies the recently determined S configuration at the spirocyclic carbon. Second, the distortion of the DNA duplex is similar to that of the single-oxidation product 8-oxoguanine. For both oxidized lesions, adaptation of the syn conformation results in similar backbone distortions in the DNA duplex. The resulting conformation positions the dSp1 A-ring as the base-pairing face whereas the B-ring of dSp1 protrudes into the major groove.
在DNA聚合酶β活性位点的背景下获得了螺环亚氨基二氢嘧啶（dSp1）的首个高分辨率晶体结构，该结构揭示了两个重要区域。首先，该结构验证了最近确定的螺环碳上的S构型。其次，DNA双链体的扭曲与单氧化产物8-氧代鸟嘌呤的扭曲相似。对于这两种氧化损伤，顺式构象的适应导致DNA双链体中出现相似的主链扭曲。由此产生的构象将dSp1的A环定位为碱基配对面，而dSp1的B环则突出进入大沟。
