title: Dynamic determination of the functional state in photolyase and the implication for cryptochrome.
abstract: The flavin adenine dinucleotide cofactor has an unusual bent configuration in photolyase and cryptochrome, and such a folded structure may have a functional role in initial photochemistry. Using femtosecond spectroscopy, we report here our systematic characterization of cyclic intramolecular electron transfer (ET) dynamics between the flavin and adenine moieties of flavin adenine dinucleotide in four redox forms of the oxidized, neutral, and anionic semiquinone, and anionic hydroquinone states. By comparing wild-type and mutant enzymes, we have determined that the excited neutral oxidized and semiquinone states absorb an electron from the adenine moiety in 19 and 135 ps, whereas the excited anionic semiquinone and hydroquinone states donate an electron to the adenine moiety in 12 ps and 2 ns, respectively. All back ET dynamics occur ultrafast within 100 ps. These four ET dynamics dictate that only the anionic hydroquinone flavin can be the functional state in photolyase due to the slower ET dynamics (2 ns) with the adenine moiety and a faster ET dynamics (250 ps) with the substrate, whereas the intervening adenine moiety mediates electron tunneling for repair of damaged DNA. Assuming ET as the universal mechanism for photolyase and cryptochrome, these results imply anionic flavin as the more attractive form of the cofactor in the active state in cryptochrome to induce charge relocation to cause an electrostatic variation in the active site and then lead to a local conformation change to initiate signaling.
authors.affiliation: Department of Physics, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Zheyun
authors.initials: Z
authors.lastname: Liu
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.forename: Xunmin
authors.initials: X
authors.lastname: Guo
authors.forename: Chuang
authors.initials: C
authors.lastname: Tan
authors.forename: Jiang
authors.initials: J
authors.lastname: Li
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wang
authors.forename: Aziz
authors.initials: A
authors.lastname: Sancar
authors.forename: Dongping
authors.initials: D
authors.lastname: Zhong
mesh_terms: D000225:Adenine / Q000737:chemistry / Q000378:metabolism; D016227:Benzoquinones / Q000737:chemistry / Q000378:metabolism; D056931:Cryptochromes / Q000737:chemistry* / Q000378:metabolism; D004255:Deoxyribodipyrimidine Photo-Lyase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004579:Electron Transport / Q000528:radiation effects; D004735:Energy Transfer; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D005182:Flavin-Adenine Dinucleotide / Q000737:chemistry / Q000378:metabolism; D005415:Flavins / Q000737:chemistry / Q000378:metabolism; D006873:Hydroquinones / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D009154:Mutation; D010084:Oxidation-Reduction / Q000528:radiation effects; D055668:Photochemical Processes; D013053:Spectrophotometry; D013379:Substrate Specificity; D013997:Time Factors; D014364:Tryptophan / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D016227:Benzoquinones; D056931:Cryptochromes; D029968:Escherichia coli Proteins; D005415:Flavins; D006873:Hydroquinones; C001922:lumiflavin; D005182:Flavin-Adenine Dinucleotide; C025232:semiquinone radicals; D014364:Tryptophan; D004255:Deoxyribodipyrimidine Photo-Lyase; D000225:Adenine; C031927:hydroquinone
keywords: adenine electron acceptor; adenine electron donor; femtosecond dynamics; flavin functional state; intracofactor electron transfer