Role of Adenine in Thymine-Dimer Repair by Reduced Flavin-Adenine Dinucleotide

Li, Guifeng; Sichula, Vincent; Glusac, Ksenija D.

doi:10.1021/jp804506t

Cited by 18 publications

(26 citation statements)

References 42 publications

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“…1) [9]. Although the kinetics of DNA repair have been elucidated by our group [10] and others [11][12][13][14][15], the role played by this unusual FAD conformation in the electron transfer pathway is still unclear [16][17][18][19]. We have addressed the role of the FAD adenine in DNA repair by replacing it with 1,N 6 -ethenoadenine (εAde) through the chemical modification of FAD (εFAD, see Fig.…”

Section: Introductionmentioning

confidence: 99%

Comparing ultrafast excited state quenching of flavin 1,N6-ethenoadenine dinucleotide and flavin adenine dinucleotide by optical spectroscopy and DFT calculations

Morris

Barnard

Narayanan

et al. 2022

Photochem Photobiol Sci

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Flavins are photoenzymatic cofactors often exploiting the absorption of light to energize photoinduced redox chemistry in a variety of contexts. Both flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) are used for this function. The study of these photoenzymes has been facilitated using flavin analogs. Most of these analogs involve modification of the flavin ring, and there is recent evidence that adenine (Ade)-modified FAD can affect enzyme turnover, but so far this has only been shown for enzymes where the adenine and flavin rings are close to each other in a stacked conformation. FAD is also stacked in aqueous solution, and its photodynamics are quite different from unstacked FAD or FMN. Oxidized photoexcited FAD decays rapidly, presumably through PET with Ade as donor and Fl* as acceptor. Definitive identification of the spectral signatures of Ade •+ and Fl •− radicals is elusive. Here we use the FAD analog Flavin 1,N 6 -Ethenoadenine Dinucleotide (εFAD) to study how different photochemical outcomes depend on the identity of the Ade moiety in stacked FAD and its analog εFAD. We have used UV-Vis transient absorption spectroscopy complemented by TD-DFT calculations to investigate the excited state evolution of the flavins. In FAD*, no radicals were observed, suggesting that FAD* does not undergo PET. εFAD* kinetics showed a broad absorption band that suggests a charge transfer state exists upon photoexcitation with evidence for radical pair formation. Surprisingly, significant triplet flavin was produced from εFAD* We hypothesize that the dipolar (ε)Ade moieties differentially modulate the singlet-triplet energy gap, resulting in different intersystem crossing rates. The additional electron density on the etheno group of εFAD supplies better orbital overlap with the flavin S 1 state, accelerating charge transfer in that molecule.

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Section: Introductionmentioning

confidence: 99%

Comparing ultrafast excited state quenching of flavin 1,N6-ethenoadenine dinucleotide and flavin adenine dinucleotide by optical spectroscopy and DFT calculations

Morris

Barnard

Narayanan

et al. 2022

Photochem Photobiol Sci

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“…1 Even though most of the flavoproteins are not light-driven, several flavoprotein photoreceptors have been recently discovered, and the mechanism of their switching behavior, investigated. 2 To better understand the mechanism of light-driven catalysis by flavoproteins, we 3,4 and others 5,6 have studied excited-state behavior of flavin cofactors in aqueous solution. One of the findings of this research is that flavin-adenine dinucleotide (FAD) in aqueous solution exhibits significantly shorter excitedstate lifetime than its analog, flavin-mononucleotide.…”

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confidence: 99%

The Role of Adenine in Fast Excited-State Deactivation of FAD: a Femtosecond Mid-IR Transient Absorption Study

Glusac

2009

J. Phys. Chem. B

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We present a study of excited-state dynamics of two flavin cofactors: flavin-adenine dinucleotide (FAD) and flavin-mononucleotide (FMN). We used femtosecond mid-R transient absorption spectroscopy to study the effect of FAD conformation on its excited-state behavior. The conformation of FAD was modulated by changing the solvent polarity: in D(2)O, FAD is present predominantly in the "stacked" conformation, in which flavin and adenine moieties are in close proximity to each other, whereas the increased amount of DMSO led to an increased amount of the "open" conformer. FMN served as a model system which lacks adenine. We found that the "stacked" conformer undergoes an intramolecular photoinduced electron transfer from adenine to flavin with the forward electron transfer rate of k(f) = 1.9.10(11) s(-1) and the geminate recombination rate of k(b) = 1.1.10(11) s(-1). In the case of the "open" conformer, no intramolecular electron transfer was observed.

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“…As noted above, the two very recent TA studies of Brettel and Zhong confirm this assignment. However, in 2008, Li and Glusac saw a difference of repair rate constants for bimolecular collisions between a CPD substrate and *FADH − vs *FMNH − giving convincing evidence that PET to the Ade was important for these model systems, although this may be due to adenine:dimer alignment effects rather than changes in the electron transfer pathway due to the adenine.…”

Section: Discussionmentioning

confidence: 99%

An Ethenoadenine FAD Analog Accelerates UV Dimer Repair by DNA Photolyase

Narayanan

Singh

Kodali

et al. 2017

Photochem & Photobiology

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Reduced anionic flavin adenine dinucleotide (FADH ) is the critical cofactor in DNA photolyase (PL) for the repair of cyclobutane pyrimidine dimers (CPD) in UV-damaged DNA. The initial step involves photoinduced electron transfer from *FADH to the CPD. The adenine (Ade) moiety is nearly stacked with the flavin ring, an unusual conformation compared to other FAD-dependent proteins. The role of this proximity has not been unequivocally elucidated. Some studies suggest that Ade is a radical intermediate, but others conclude that Ade modulates the electron transfer rate constant (k ) through superexchange. No study has succeeded in removing or modifying this Ade to test these hypotheses. Here, FAD analogs containing either an ethano- or etheno-bridged Ade between the AN1 and AN6 atoms (e-FAD and ε-FAD, respectively) were used to reconstitute apo-PL, giving e-PL and ε-PL respectively. The reconstitution yield of e-PL was very poor, suggesting that the hydrophobicity of the ethano group prevented its uptake, while ε-PL showed 50% reconstitution yield. The substrate binding constants for ε-PL and rPL were identical. ε-PL showed a 15% higher steady-state repair yield compared to FAD-reconstituted photolyase (rPL). The acceleration of repair in ε-PL is discussed in terms of an ε-Ade radical intermediate vs superexchange mechanism.

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Role of Adenine in Thymine-Dimer Repair by Reduced Flavin-Adenine Dinucleotide

Cited by 18 publications

References 42 publications

Comparing ultrafast excited state quenching of flavin 1,N6-ethenoadenine dinucleotide and flavin adenine dinucleotide by optical spectroscopy and DFT calculations

Comparing ultrafast excited state quenching of flavin 1,N6-ethenoadenine dinucleotide and flavin adenine dinucleotide by optical spectroscopy and DFT calculations

The Role of Adenine in Fast Excited-State Deactivation of FAD: a Femtosecond Mid-IR Transient Absorption Study

An Ethenoadenine FAD Analog Accelerates UV Dimer Repair by DNA Photolyase

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