含有顺式-环丁烷胸腺嘧啶二聚体损伤的DNA的基本动力学
Essential dynamics of DNA containing a cis.syn cyclobutane thymine dimer lesion.
作者信息
Yamaguchi H, van Aalten D M, Pinak M, Furukawa A, Osman R
机构信息
Space and Particle Radiation Science Research Group, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ku, Chiba 263, Japan.
出版信息
Nucleic Acids Res. 1998 Apr 15;26(8):1939-46. doi: 10.1093/nar/26.8.1939.
Conformational properties of a UV-damaged DNA decamer containing a cis.syn cyclobutane thymine dimer (PD) have been investigated by molecular dynamics (MD) simulations. Results from MD simulations of the damaged decamer DNA show a kink of approximately 21.7 degrees at the PD damaged site and a disruption of H bonding between the 5'-thymine of the PD and its complementary adenine. However, no extra-helical flipping of the 3'-adenine complementary to the PD was observed. Comparison to two undamaged DNA decamers, one with the same sequence and the other with an AT replacing the TT sequence, indicates that these properties are specific to the damaged DNA. Essential dynamics (ED) derived from the MD trajectories of the three DNAs show that the backbone phosphate between the two adenines complementary to the PD of the damaged DNA has considerably larger mobility than the rest of the molecule and occurs only in the damaged DNA. As observed in the crystal structure of T4 endonuclease V in a complex with the damaged DNA, the interaction of the enzyme with the damaged DNA can lead to bending along the flexible joint and to induction of adenine flipping into an extra-helical position. Such motions may play an important role in damage recognition by repair enzymes.
通过分子动力学（MD）模拟研究了含有顺式 - 反式环丁烷胸腺嘧啶二聚体（PD）的紫外线损伤DNA十聚体的构象性质。受损十聚体DNA的MD模拟结果显示，在PD损伤位点有一个约21.7度的扭结，并且PD的5'-胸腺嘧啶与其互补腺嘌呤之间的氢键被破坏。然而，未观察到与PD互补的3'-腺嘌呤的额外螺旋翻转。与两个未受损的DNA十聚体进行比较，一个具有相同序列，另一个用AT取代TT序列，结果表明这些性质是受损DNA所特有的。从三个DNA的MD轨迹导出的主成分动力学（ED）表明，与受损DNA的PD互补的两个腺嘌呤之间的主链磷酸具有比分子其余部分大得多的流动性，并且仅在受损DNA中出现。正如在与受损DNA形成复合物的T4内切核酸酶V的晶体结构中所观察到的，酶与受损DNA的相互作用可导致沿柔性接头弯曲并诱导腺嘌呤翻转到额外螺旋位置。这种运动可能在修复酶识别损伤中起重要作用。
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