title: Photoselected electron transfer pathways in DNA photolyase.
abstract: 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.
authors.affiliation: Departments of Chemistry and Biochemistry, Duke University, Durham, NC 27708, USA.
authors.forename: Tatiana R
authors.initials: TR
authors.lastname: Prytkova
authors.forename: David N
authors.initials: DN
authors.lastname: Beratan
authors.forename: Spiros S
authors.initials: SS
authors.lastname: Skourtis
mesh_terms: D003198:Computer Simulation; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004255:Deoxyribodipyrimidine Photo-Lyase / Q000737:chemistry* / Q000378:metabolism*; D019281:Dimerization; D004583:Electrons; D004926:Escherichia coli / Q000201:enzymology; D008958:Models, Molecular; D010777:Photochemistry; D017434:Protein Structure, Tertiary
chemical_list: D004247:DNA; D004255:Deoxyribodipyrimidine Photo-Lyase