title: Excited-state proton coupled electron transfer between photolyase and the damaged DNA through water wire: a photo-repair mechanism.
abstract: The photolyase enzyme absorbs blue light to repair damaged DNA through a cyclic electron transfer reaction. A description of the underlying mechanism has proven to be a challenging issue for both experimental and theoretical studies. In the present work, combined CASPT2//CASSCF/AMBER (QM/MM) calculations have been performed for damaged DNA in photolyase. A proton-coupled electron transfer (PCET) mechanism has been determined for restoring cyclobutane pyrimidine dimer (CPD) to two normal thymine bases by irradiation of photolyase. A well-defined water wire between FADH(-) and CPD was determined as a bridge to assist the PCET process within FADH(-) and thereby trigger the forward electron transfer to CPD. The subsequent CPD splitting and the alternation of the H-bond pattern proceed in a concerted way, which makes the productive backward electron transfer occur on an ultrafast timescale. A local minimum of SCT((1)ππ*)-LMin was identified on the pathway of the futile backward electron transfer (BET), which is stabilized by the strong H-bond interaction between the water wire and CPD. As a result, the futile BET process is endothermic by ∼18.0 kcal mol(-1), which is responsible for a 2.4 ns timescale inferred experimentally for the futile BET process. Besides the unbiased interpretation for the majority of the experimental findings, the present study provides a new excited-state PCET mechanism, which leads to a significant step toward a deeper understanding of the photo-repair process of damaged-DNA by the photolyase enzyme.
authors.affiliation: Key Laboratory of Theoretical and Computational Photochemistry of Ministry of Education, Department of Chemistry, Beijing Normal University, Xin-wai-da-jie No. 19, Beijing, 100875, China. xuebochen@bnu.edu.cn fangwh@bnu.edu.cn.
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Wang
authors.forename: Xuebo
authors.initials: X
authors.lastname: Chen
authors.forename: Weihai
authors.initials: W
authors.lastname: Fang
mesh_terms: D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004255:Deoxyribodipyrimidine Photo-Lyase / Q000737:chemistry* / Q000378:metabolism; D004579:Electron Transport; D006860:Hydrogen Bonding; D008027:Light; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D011522:Protons; D011789:Quantum Theory; D014867:Water / Q000737:chemistry* / Q000378:metabolism
chemical_list: D011522:Protons; D014867:Water; D004247:DNA; D004255:Deoxyribodipyrimidine Photo-Lyase