The sacrificial inactivation of the blue-light photosensor cryptochrome from <i>Drosophila melanogaster</i>

Kutta, Roger Jan; Archipowa, Nataliya; Scrutton, Nigel S.

doi:10.1039/c8cp04671a

Cited by 21 publications

(32 citation statements)

References 52 publications

(75 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As this synthetic method did not allow the synthesis of the phenyl derivative 5, route B was developed. In this three-component microwave-assisted procedure, adapted from Tu et al 49 , compound 5 was obtained from a reaction of benzaldehyde with N-butyl-3,4-dimethoxyaniline (7) and N-methylbarbituric acid (9). Following this procedure, the phenyl derivative could be isolated in both the oxidised (5 ox ) and fully reduced form (5 red ), which reflects the low sensitivity of the dFl red against O 2 3,50 .…”

Section: Resultsmentioning

confidence: 99%

“…Flavins (Fls) form semiquinones (Fl sq s) ( Fig. 1b), which are transiently stable in solution 6 and more stable in protein environments 7,8 . Fl sq s are typically involved in one-electron redox processes 1,9 .…”

mentioning

confidence: 99%

“…Fl cofactors in their fully reduced form participate in photo-induced electron transfer (PET) reactions in DNA photolyases repairing pyrimidine dimers formed upon exposure to ultraviolet (UV) light 23,24 . Fls in their oxidised form are responsible for bacterial bioluminescence 25 or perform various functions in photoreceptors 7,[26][27][28] . dFl dF 0 in its oxidised form serves as a light-harvesting antenna in photolyases 29 .…”

mentioning

confidence: 99%

See 2 more Smart Citations

Deazaflavin reductive photocatalysis involves excited semiquinone radicals

et al. 2020

Self Cite

View full text Add to dashboard Cite

Flavin-mediated photocatalytic oxidations are established in synthetic chemistry. In contrast, their use in reductive chemistry is rare. Deazaflavins with a much lower reduction potential are even better suited for reductive chemistry rendering also deazaflavin semiquinones as strong reductants. However, no direct evidence exists for the involvement of these radical species in reductive processes. Here, we synthesise deazaflavins with different substituents at C5 and demonstrate their photocatalytic activity in the dehalogenation of p-halogenanisoles with best performance under basic conditions. Mechanistic investigations reveal a consecutive photo-induced electron transfer via the semiquinone form of the deazaflavin as part of a triplet-correlated radical pair after electron transfer from a sacrificial electron donor to the triplet state. A second electron transfer from the excited semiquinone to p-halogenanisoles triggers the final product formation. This study provides first evidence that the reductive power of excited deazaflavin semiquinones can be used in photocatalytic reductive chemistry.

show abstract

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Deazaflavin reductive photocatalysis involves excited semiquinone radicals

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Conformational change in the dCRY CTT correlates with photoreduction of the flavin to the ASQ 12 – 15 . Alterations to a conserved tetrad of tryptophan residues that supply electrons to the photoexcited flavin 24 , 25 affect dCRY photoreduction rates, dCRY light stability, and TIM degradation activity 26 . However, some studies have found that Phe substitutions in the Trp tetrad that do not photoreduce retain activity in several assays 12 , 27 – 29 .…”

Section: Introductionmentioning

confidence: 99%

Tuning flavin environment to detect and control light-induced conformational switching in Drosophila cryptochrome

et al. 2021

View full text Add to dashboard Cite

Light-induction of an anionic semiquinone (SQ) flavin radical in Drosophila cryptochrome (dCRY) alters the dCRY conformation to promote binding and degradation of the circadian clock protein Timeless (TIM). Specific peptide ligation with sortase A attaches a nitroxide spin-probe to the dCRY C-terminal tail (CTT) while avoiding deleterious side reactions. Pulse dipolar electron-spin resonance spectroscopy from the CTT nitroxide to the SQ shows that flavin photoreduction shifts the CTT ~1 nm and increases its motion, without causing full displacement from the protein. dCRY engineered to form the neutral SQ serves as a dark-state proxy to reveal that the CTT remains docked when the flavin ring is reduced but uncharged. Substitutions of flavin-proximal His378 promote CTT undocking in the dark or diminish undocking in the light, consistent with molecular dynamics simulations and TIM degradation activity. The His378 variants inform on recognition motifs for dCRY cellular turnover and strategies for developing optogenetic tools.

show abstract

“…MD simulations have also suggested for the FAD cofactor roles other than photoreduction and CRY activation: the FAD presence would confer to the receptor a more fluctuation-prone behavior, thus decreasing the amount of necessary light input energy for CRY activation (Masiero et al, 2014). Recent studies performed on a longer timescale have revealed that following photoactivation, FAD is released from the FAD-binding pocket, providing evidence that CRY undergoes an inactivation reaction rather than a photocycle (Kutta et al, 2018), in agreement with the reported irreversible nature of the light-induced conformational changes (Ozturk et al, 2009;Kattnig et al, 2018;Lin et al, 2018). The active form of CRY is then able to bind the circadian components TIMELESS (Ceriani et al, 1999) and PERIOD (Rosato et al, 2001).…”

Section: Structure and Photoactivationmentioning

confidence: 99%