The flavin redox-system and its biological function

Müller, Franz

doi:10.1007/3-540-11846-2_3

Cited by 84 publications

(30 citation statements)

References 222 publications

(29 reference statements)

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“…Flavin can have three different redox states: oxidized form, one-electron reduced radical semiquinone, and two-electron fully reduced hydroquinone. Semiquinone and hydroquinone have p K a values of 8.3 and 6.7, respectively, 40 and can be present in their neutral or anionic forms under physiological conditions. Among the five redox forms, two redox pairs, oxidized flavin/anionic semiquinone (FAD/FAD •− ) and neutral semiquinone/anionic hydroquinone (FADH • /FADH − ), are often involved in intermolecular ET reactions.…”

Section: Absorption and Emission Spectra Of Flavins In Various Redmentioning

confidence: 99%

Dynamics and mechanisms of DNA repair by photolyase

Liu

Wang

Zhong

2015

Phys. Chem. Chem. Phys.

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Photolyase, a class of flavoproteins, uses blue light to repair two types of ultraviolet-induced DNA damage, cyclobutane pyrimidine dimer (CPD) and pyrimidine-pyrimidone (6–4) photoproduct (6–4PP). In this perspective, we review the recent progress on the repair dynamics and mechanisms of both types of DNA restoration by photolyases. We first report the spectroscopic characterization of flavin in various redox states and the active-site solvation dynamics in photolyases. We then systematically summarize the detailed repair dynamics of damaged DNA by photolyases and a biomimetic system through resolving all elementary steps on the ultrafast timescales, including multiple intermolecular electron- and proton-transfer reactions and bond-breaking and -making processes. We determined the unique electron tunneling pathways, identified the key functional residues and revealed the molecular origin of high repair efficiency, and thus elucidate the molecular mechanisms and repair photocycles at the most fundamental level. We finally conclude that the active sites of photolyases, unlike aqueous solution for the biomimetic system, provide a unique electrostatic environment and local flexibility and thus a dedicated synergy for all elementary dynamics to maximize the repair efficiency. This repair photomachine is the first enzyme that the entire functional evolution is completely mapped out in real time.

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Section: Absorption and Emission Spectra Of Flavins In Various Redmentioning

confidence: 99%

Dynamics and mechanisms of DNA repair by photolyase

Liu

Wang

Zhong

2015

Phys. Chem. Chem. Phys.

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“…They can exist in three different redox states: oxidized, one-electron reduced (semiquinone), and two-electron reduced (hydroquinone). Semiquinone and hydroquinone have p K a values of 8.3 and 6.7, respectively [46], and can be present in their neutral or anionic forms under physiological conditions. Due to their unique ability to participate in both one- and two-electron transfer processes, flavins are often involved in intermolecular electron transfer (ET) reactions, and flavoproteins are ubiquitous in biological systems and participate in a broad spectrum of key biological processes that rely on enzyme-mediated oxido-reduction reactions [42–44, 47–50].…”

Section: Introductionmentioning

confidence: 99%

“…Among the five redox forms, two redox pairs, oxidized flavin/anionic semiquinone (FAD/FAD •− ) and neutral semiquinone/anionic hydroquinone (FADH • /FADH − ), exist in photolyase/cryptochromes. The four states are convertible under physiological conditions through intraprotein ET and proton transfer (PT) [46] and can be spectrally differentiated by their distinct UV-vis absorptions (Fig. 2B).…”

Section: Introductionmentioning

confidence: 99%

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Photolyase: Dynamics and electron-transfer mechanisms of DNA repair

Zhang

Wang

Zhong

2017

Archives of Biochemistry and Biophysics

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Photolyase, a flavoenzyme containing flavin adenine dinucleotide (FAD) molecule as a catalytic cofactor, repairs UV-induced DNA damage of cyclobutane pyrimidine dimer (CPD) and pyrimidine-pyrimidone (6-4) photoproduct using blue light. The FAD cofactor, conserved in the whole protein superfamily of photolyase/cryptochromes, adopts a unique folded configuration at the active site that plays a critical functional role in DNA repair. Here, we review our comprehensive characterization of the dynamics of flavin cofactor and its repair photocycles by different classes of photolyases on the most fundamental level. Using femtosecond spectroscopy and molecular biology, significant advances have recently been made to map out the entire dynamical evolution and determine actual timescales of all the catalytic processes in photolyases. The repair of CPD reveals seven electron-transfer (ET) reactions among ten elementary steps by a cyclic ET radical mechanism through bifurcating ET pathways, a direct tunneling route mediated by the intervening adenine and a two-step hopping path bridged by the intermediate adenine from the cofactor to damaged DNA, through the conserved folded flavin at the active site. The unified, bifurcated ET mechanism elucidates the molecular origin of various repair quantum yields of different photolyases from three life kingdoms. For 6-4 photoproduct repair, a similar cyclic ET mechanism operates and a new cyclic proton transfer with a conserved histidine residue at the active site of (6-4) photolyases is revealed.

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“…The redox potentials of both electron transfer steps vary largely among different flavoproteins and depend on the chemical nature of the active site in which the isoalloxazine resides. This property makes the flavin suitable as an electron shuttle in very different redox reactions which explains its widespread occurrence in nature (Muller, 1983). The role of the protein environment in modifying the chemical reactions and the redox properties of the flavin is not yet clear.…”

mentioning

confidence: 99%

Monoclonal Antibodies Against Two Electron Reduced Riboflavin and a Quantification of Affinity Constants for this Oxygen‐Sensitive Molecule

Bruggeman

Schoenmakers

Schots³

et al. 1995

European Journal of Biochemistry

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In order to create a protein environment that binds preferentially to the two-electron reduced form of flavin, monoclonal antibodies have been raised against a reduced flavin derivative. Due to the low fluorescence quantum yield and visible light absorption and to the instability of reduced flavin in an aerobic environment, it is not possible to determine the affinities of these antibodies for two-electron-reduced flavin using standard techniques. Because of its sensitivity, time-resolved fluorescence can be used to overcome this problem. This technique has been applied to study the binding of two antibodies, an IgG, and an IgM, to reduced riboflavin (1,5dihydroriboflavin) and oxidized riboflavin (riboflavin). The affinity of the IgC, is more than 80 times larger for 1,s-dihydroriboflavin than for riboflavin. From analysis of the dynamical parameters of the system it is apparent that the internal motion of 1,5-dihydroriboflavin bound to IgG, is much more restricted than that of riboflavin. In contrast, the affinity of the IgM is only slightly higher for 1,5-dihydroriboflavin than for riboflavin and the flexibility of binding of both flavin redox states in the antigen binding site is almost similar.Keywords; monoclonal antibodies ; time-resolved fluorescence ; maximum-entropy analysis ; reduced riboflavin; affinity constants.Flavins mediate a variety of chemical reactions including dehydrogenation, electron transfer, activation of molecular oxygen and photochemical reactions. This versatility sets flavoproteins apart from most other cofactor-dependent enzymes, which, in general, each catalyze a single type of reaction (Ghisla and Massey, 1989). One of the most interesting features of the versatile flavin molecule consists of its redox properties which can be modulated by the (protein) environment. The redox active part of the flavin is the isoalloxazine ring which can exist in oxidized flavoquinone, one-electron-reduced flavosemiquinone and two-electron-reduced flavohydroquinone states. The redox potentials of both electron transfer steps vary largely among different flavoproteins and depend on the chemical nature of the active site in which the isoalloxazine resides. This property makes the flavin suitable as an electron shuttle in very different redox reactions which explains its widespread occurrence in nature (Muller, 1983). The role of the protein environment in modifying the chemical reactions and the redox properties of the flavin is not yet clear. Creating artificial protein environments with a predetermined affinity for oxidized and reduced flavin and comparing the structural and redox properties of these proteins, might contribute to obtaining more insight to this problem. Monoclonal antibodies (mAbs) are very useful tools for this because the flavoquinone differs from the hydroquinone in its conformation and electronic properties. This enables the generation of antibodies specific for either the reduced or the oxidized form. Shokat et al. (1988) have indeed shown that I t is possible to create an anti-...

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The flavin redox-system and its biological function

Cited by 84 publications

References 222 publications

Dynamics and mechanisms of DNA repair by photolyase

Dynamics and mechanisms of DNA repair by photolyase

Photolyase: Dynamics and electron-transfer mechanisms of DNA repair

Monoclonal Antibodies Against Two Electron Reduced Riboflavin and a Quantification of Affinity Constants for this Oxygen‐Sensitive Molecule

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