Prytkova Tatiana R, Beratan David N, Skourtis Spiros S
Departments of Chemistry and Biochemistry, Duke University, Durham, NC 27708, USA.
Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):802-7. doi: 10.1073/pnas.0605319104. Epub 2007 Jan 5.
Cyclobutane dimer photolyases are proteins that bind to UV-damaged DNA containing cyclobutane pyrimidine dimer lesions. They repair these lesions by photo-induced electron transfer. The electron donor cofactor of a photolyase is a two-electron-reduced flavin adenine dinucleotide (FADH(-)). When FADH(-) is photo-excited, it transfers an electron from an excited pi --> pi* singlet state to the pyrimidine dimer lesion of DNA. We compute the lowest excited singlet states of FADH(-) using ab initio (time-dependent density functional theory and time-dependent Hartree-Fock), and semiempirical (INDO/S configuration interaction) methods. The calculations show that the two lowest pi --> pi* singlet states of FADH(-) are localized on the side of the flavin ring that is proximal to the dimer lesion of DNA. For the lowest-energy donor excited state of FADH(-), we compute the conformationally averaged electronic coupling to acceptor states of the thymine dimer. The coupling calculations are performed at the INDO/S level, on donor-acceptor cofactor conformations obtained from molecular dynamics simulations of the solvated protein with a thymine dimer docked in its active site. These calculations demonstrate that the localization of the (1)FADH(-)* donor state on the flavin ring enhances the electronic coupling between the flavin and the dimer by permitting shorter electron-transfer pathways to the dimer that have single through-space jumps. Therefore, in photolyase, the photo-excitation itself enhances the electron transfer rate by moving the electron towards the dimer.
环丁烷二聚体光解酶是一种与含有环丁烷嘧啶二聚体损伤的紫外线损伤DNA结合的蛋白质。它们通过光诱导电子转移来修复这些损伤。光解酶的电子供体辅因子是双电子还原的黄素腺嘌呤二核苷酸（FADH(-)）。当FADH(-)受到光激发时，它会将一个电子从激发的π→π单重态转移到DNA的嘧啶二聚体损伤处。我们使用从头算方法（含时密度泛函理论和含时哈特里-福克方法）以及半经验方法（INDO/S组态相互作用方法）计算FADH(-)的最低激发单重态。计算结果表明，FADH(-)的两个最低π→π单重态位于黄素环靠近DNA二聚体损伤的一侧。对于FADH(-)的最低能量供体激发态，我们计算了其与胸腺嘧啶二聚体受体态的构象平均电子耦合。耦合计算是在INDO/S水平上进行的，所使用的供体-受体辅因子构象是通过对结合有胸腺嘧啶二聚体的溶剂化蛋白质进行分子动力学模拟得到的。这些计算表明，FADH(-)*供体态在黄素环上进行定位，通过允许更短的单重空间跳跃的电子转移途径到达二聚体，增强了黄素与二聚体之间的电子耦合。因此，在光解酶中，光激发本身通过将电子移向二聚体来提高电子转移速率。
