Conformation of the Flavin Adenine Dinucleotide Cofactor FAD in DNA-Photolyase: A Molecular Dynamics Study

Hahn, Jutta; Michel‐Beyerle, M. E.; Rösch, Notker

doi:10.1007/s008940050133

Cited by 28 publications

(45 citation statements)

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“…Figure 4 shows the entire energy profile of the enzymatic repair along the reaction coordinate with at least six fundamental steps including the excited-state deactivation, three ET elementary reactions and two sequential bond breaking and making processes. To maximize the repair efficiency, the enzyme has a relatively rigid active site, structurally and electrostatically, to avoid the ultrafast deactivation from the butterfly bending motion and lengthen the excited-state lifetime 27,28 , and a favourable redox environment to lead to an appropriate FET, not too slow so as to result in lower F FET and not too fast so as to cause faster BET with a lower F SP2 . After charge separation, the reaction proceeds to the ultrafast C5-C5 0 bond splitting, thus eliminating the first intact charge-recombination channel to the original ground state without the dimer splitting.…”

Section: Discussionmentioning

confidence: 99%

The molecular origin of high DNA-repair efficiency by photolyase

Tan

Liu

et al. 2015

Nat Commun

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The primary dynamics in photomachinery such as charge separation in photosynthesis and bond isomerization in sensory photoreceptor are typically ultrafast to accelerate functional dynamics and avoid energy dissipation. The same is also true for the DNA repair enzyme, photolyase. However, it is not known how the photoinduced step is optimized in photolyase to attain maximum efficiency. Here, we analyse the primary reaction steps of repair of ultraviolet-damaged DNA by photolyase using femtosecond spectroscopy. With systematic mutations of the amino acids involved in binding of the flavin cofactor and the cyclobutane pyrimidine dimer substrate, we report our direct deconvolution of the catalytic dynamics with three electron-transfer and two bond-breaking elementary steps and thus the fine tuning of the biological repair function for optimal efficiency. We found that the maximum repair efficiency is not enhanced by the ultrafast photoinduced process but achieved by the synergistic optimization of all steps in the complex repair reaction.

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Section: Discussionmentioning

confidence: 99%

The molecular origin of high DNA-repair efficiency by photolyase

Tan

Liu

et al. 2015

Nat Commun

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“…The sensitivity analysis has shown that despite the close proximity of the dimer to FADH\ in the catalytic site, the electron transfer mechanism between the #avin and the pyrimidine bases is not direct, but indirect, with the adenine acting as an intermediate. Such a mode of electron transfer utilizes the unusual conformation of FADH\ in photolyases, which brings the isoalloxazine ring of the #avin and adenine in close proximity (Park et al, 1995;Tamada et al, 1997;Hahn et al, 1998), and the peculiar features of the docked orientation of the dimer in the catalytic site.…”

Section: Introductionmentioning

confidence: 99%

DNA Repair Mechanism by Photolyase: Electron Transfer Path from the Photolyase Catalytic Cofactor FADH−to DNA Thymine Dimer

Medvedev

Stuchebrukhov

2001

Journal of Theoretical Biology

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“…In addition, the DNA dimer is flipped out of the DNA helix and approaches the FAD cofactor (5,16), but the distance between the DNA substrate and FAD cofactor is not certain. Theoretical studies (17)(18)(19), with one exception (20), have predicted that the distance between them precludes van der Waals interactions. A long distance between FAD and the DNA substrate was also suggested by analysis of the electric dipole moment (21) and by EPR and electron nuclear double resonance (22).…”

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confidence: 99%

Similarities and Differences between Cyclobutane Pyrimidine Dimer Photolyase and (6-4) Photolyase as Revealed by Resonance Raman Spectroscopy

Uchida

Todo

et al. 2006

Journal of Biological Chemistry

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The cyclobutane pyrimidine dimer (CPD) and (6-4) photoproduct, two major types of DNA damage caused by UV light, are repaired under illumination with near UV-visible light by CPD and (6-4) photolyases, respectively. To understand the mechanism of DNA repair, we examined the resonance Raman spectra of complexes between damaged DNA and the neutral semiquinoid and oxidized forms of (6-4) and CPD photolyases. The marker band for a neutral semiquinoid flavin and band I of the oxidized flavin, which are derived from the vibrations of the benzene ring of FAD, were shifted to lower frequencies upon binding of damaged DNA by CPD photolyase but not by (6-4) photolyase, indicating that CPD interacts with the benzene ring of FAD directly but that the (6-4) photoproduct does not. Bands II and VII of the oxidized flavin and the 1398/1391 cm(-1) bands of the neutral semiquinoid flavin, which may reflect the bending of U-shaped FAD, were altered upon substrate binding, suggesting that CPD and the (6-4) photoproduct interact with the adenine ring of FAD. When substrate was bound, there was an upshifted 1528 cm(-1) band of the neutral semiquinoid flavin in CPD photolyase, indicating a weakened hydrogen bond at N5-H of FAD, and band X seemed to be downshifted in (6-4) photolyase, indicating a weakened hydrogen bond at N3-H of FAD. These Raman spectra led us to conclude that the two photolyases have different electron transfer mechanisms as well as different hydrogen bonding environments, which account for the higher redox potential of CPD photolyase.

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Conformation of the Flavin Adenine Dinucleotide Cofactor FAD in DNA-Photolyase: A Molecular Dynamics Study

Cited by 28 publications

References 0 publications

The molecular origin of high DNA-repair efficiency by photolyase

The molecular origin of high DNA-repair efficiency by photolyase

DNA Repair Mechanism by Photolyase: Electron Transfer Path from the Photolyase Catalytic Cofactor FADH−to DNA Thymine Dimer

Similarities and Differences between Cyclobutane Pyrimidine Dimer Photolyase and (6-4) Photolyase as Revealed by Resonance Raman Spectroscopy

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