Photoselected electron transfer pathways in DNA photolyase

被引:63
作者
Prytkova, Tatiana R.
Beratan, David N. [1 ]
Skourtis, Spiros S.
机构
[1] Duke Univ, Dept Chem, Durham, NC 27708 USA
[2] Duke Univ, Dept Biochem, Durham, NC 27708 USA
[3] Univ Cyprus, Dept Phys, CY-1678 Nicosia, Cyprus
关键词
D O I
10.1073/pnas.0605319104
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Cyclobutane dimer photolyases are proteins that bind to UV-damaged DNA containing cyclobutane pyrimidine climer 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 climer 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.
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收藏
页码:802 / 807
页数:6
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