Dynamic determination of the functional state in photolyase and the implication for cryptochrome

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 electro...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2013-08, Vol.110 (32), p.12972-12977
Main Authors: Liu, Zheyun, Zhang, Meng, Guo, Xunmin, Tan, Chuang, Li, Jiang, Wang, Lijuan, Sancar, Aziz, Zhong, Dongping
Format: Article
Language:English
Subjects:
Absorptivity
Active sites
Adenine - chemistry
Adenine - metabolism
Benzoquinones - chemistry
Benzoquinones - metabolism
Biological Sciences
Cryptochromes - chemistry
Cryptochromes - metabolism
Deoxyribodipyrimidine Photo-Lyase - chemistry
Deoxyribodipyrimidine Photo-Lyase - genetics
Deoxyribodipyrimidine Photo-Lyase - metabolism
Deoxyribonucleic acid
Dimers
DNA
DNA damage
Electron transfer
Electron Transport - radiation effects
Electron tunneling
Electrons
Electrostatics
Energy Transfer
Enzymes
Escherichia coli - enzymology
Escherichia coli - genetics
Escherichia coli - metabolism
Escherichia coli Proteins - chemistry
Escherichia coli Proteins - genetics
Escherichia coli Proteins - metabolism
Flavin-Adenine Dinucleotide - chemistry
Flavin-Adenine Dinucleotide - metabolism
Flavins - chemistry
Flavins - metabolism
Hydroquinones
Hydroquinones - chemistry
Hydroquinones - metabolism
Kinetics
Models, Chemical
Models, Molecular
Molecular Conformation
Molecular Structure
Mutation
Oxidation-Reduction - radiation effects
Photochemical Processes
Physical Sciences
Spectrophotometry
Substrate Specificity
Time Factors
Tryptophan - chemistry
Tryptophan - genetics
Tryptophan - metabolism
Wavelengths
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1311077110