A Conclusive Mechanism of the Photoinduced Reaction Cascade in Blue Light Using Flavin Photoreceptors

Sadeghian, Keyarash; Bocola, Marco; Schütz, Martin

doi:10.1021/ja803726a

Cited by 101 publications

(222 citation statements)

References 76 publications

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“…A pre-equilibrated water droplet with radius 20 Å containing 5187 water molecules was used to solvate the modified BLUF domain. Starting from the solvated minimized structure the same procedure as in the previous study 33 was used to obtain an MD trajectory. For two representative snap shots initial geometry optimizations at the force field level were carried out, followed by further optimizations at the QM/MM level.…”

Section: Rof In Proteinmentioning

confidence: 99%

“…For the QM/MM geometry optimizations, a QM region quite similar to that employed in previous work 33 was chosen (cf. Fig.…”

Section: Rof In Proteinmentioning

confidence: 99%

“…Sadeghian et al presented a plausible mechanism for the formation of the signaling state based on a systematic investigation of the potential energy surface. 33,34 There is strong evidence that after photo-excitation of the locally excited (LE) state of flavin, the tyrosine -flavin charge transfer (CT) state is populated via a conical intersection. This conical intersection seam has been investigated recently in detail by Udvarhelyi and Domratcheva.…”

Section: Introductionmentioning

confidence: 99%

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Why BLUF photoreceptors with roseoflavincofactors lose their biological functionality

Merz

Sadeghian

Schütz

2011

Phys. Chem. Chem. Phys.

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The photophysics of roseoflavin in three different environments is investigated by using ab initio and quantum mechanics/molecular mechanics methods. Intramolecular charge transfer is shown to be responsible for the quenching of the fluorescence in the gas phase, and in the water environment. However, for the roseoflavin incorporated into the blue light using flavin (BLUF) protein environment (substituting the native flavin) no such deactivation is found. The conical intersection between the locally excited state of the chromophore and the charge transfer state involving the tyrosine residue, which in the native BLUF domain is responsible for initiating the photocycle, is missing for the roseoflavin substituted protein. This explains the experimental observations of the lack of any photocycle, and the loss of the biological function of the BLUF photoreceptor reported earlier.

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Section: Rof In Proteinmentioning

confidence: 99%

“…For the QM/MM geometry optimizations, a QM region quite similar to that employed in previous work 33 was chosen (cf. Fig.…”

Section: Rof In Proteinmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Why BLUF photoreceptors with roseoflavincofactors lose their biological functionality

Merz

Sadeghian

Schütz

2011

Phys. Chem. Chem. Phys.

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“…In various x-ray crystal and NMR solution structures (14)(15)(16)(17)(18)28), as well as spectroscopic (13,22,(39)(40)(41) and theoretical (42)(43)(44) studies, the dark-state orientation of Gln-63 has remained ambiguous. As illustrated in Fig.…”

Section: Structure Of the Bluf Domain Of Appamentioning

confidence: 99%

Structural Refinement of a Key Tryptophan Residue in the BLUF Photoreceptor AppA by Ultraviolet Resonance Raman Spectroscopy

Unno¹,

Kikuchi²,

Masuda³

et al. 2010

AIP Conference Proceedings

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The flavin-adenine-dinucleotide-binding BLUF domain constitutes a new class of blue-light receptors, and the N-terminal domain of AppA is a representative of this family. The BLUF domain is of special interest because it uses a rigid flavin rather than an isomerizable chromophore, such as a rhodopsin or phytochrome, for its light-activation process. Crystal and solution structures of several BLUF domains were recently obtained, and their overall structures are consistent. However, there is a key ambiguity regarding the position of a conserved tryptophan (Trp-104 in AppA), in that this residue was found either close to flavin (Trp in conformation) or exposed to the solvent (Trp out conformation). The location of Trp-104 is a crucial factor in understanding the photocycle mechanism of BLUF domains, because this residue has been shown to play an essential role in the activation of AppA. In this study, we demonstrated a Trp in conformation for the BLUF domain of AppA through direct observation of the vibrational spectrum of Trp-104 by ultraviolet resonance Raman spectroscopy, and also observed light-induced conformational and environmental changes in Trp-104. This study provides a structural basis for future investigations of the photocycle mechanism of BLUF proteins.

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“…Despite numerous experimental and computational studies (8,(13)(14)(15)(16)(17), the exact nature of the signaling state and the mechanism of long-range signaling in BLUF proteins are not well understood. The active site conformation in even the dark-adapted state is still under debate because of discrepancies in the orientations of the key active site Trp, Met, and Gln residues among different experimental crystal and solution structures of BLUF domains (18)(19)(20)(21)(22)(23)(24)(25)(26).…”

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confidence: 99%

Role of active site conformational changes in photocycle activation of the AppA BLUF photoreceptor

Goyal

Hammes‐Schiffer

2017

Proc. Natl. Acad. Sci. U.S.A.

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Blue light using flavin adenine dinucleotide (BLUF) proteins are essential for the light regulation of a variety of physiologically important processes and serve as a prototype for photoinduced proton-coupled electron transfer (PCET). Free-energy simulations elucidate the active site conformations in the AppA (activation of photopigment and puc expression) BLUF domain before and following photoexcitation. The free-energy profile for interconversion between conformations with either Trp104 or Met106 closer to the flavin, denoted Trp in /Met out and Trp out /Met in , reveals that both conformations are sampled on the ground state, with the former thermodynamically favorable by ∼3 kcal/mol. These results are consistent with the experimental observation of both conformations. To analyze the proton relay from Tyr21 to the flavin via Gln63, the free-energy profiles for Gln63 rotation were calculated on the ground state, the locally excited state of the flavin, and the charge-transfer state associated with electron transfer from Tyr21 to the flavin. For the Trp in /Met out conformation, the hydrogenbonding pattern conducive to the proton relay is not thermodynamically favorable on the ground state but becomes more favorable, corresponding to approximately half of the configurations sampled, on the locally excited state. The calculated energy gaps between the locally excited and charge-transfer states suggest that electron transfer from Tyr21 to the flavin is more facile for configurations conducive to proton transfer. When the active site conformation is not conducive to PCET from Tyr21, Trp104 can directly compete with Tyr21 for electron transfer to the flavin through a nonproductive pathway, impeding the signaling efficiency.photoreceptor | BLUF | proton transfer | electron transfer | hydrogen bonding

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A Conclusive Mechanism of the Photoinduced Reaction Cascade in Blue Light Using Flavin Photoreceptors

Cited by 101 publications

References 76 publications

Why BLUF photoreceptors with roseoflavincofactors lose their biological functionality

Why BLUF photoreceptors with roseoflavincofactors lose their biological functionality

Structural Refinement of a Key Tryptophan Residue in the BLUF Photoreceptor AppA by Ultraviolet Resonance Raman Spectroscopy

Role of active site conformational changes in photocycle activation of the AppA BLUF photoreceptor

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