Competition between two cysteines in covalent binding of biliverdin to phytochrome domains

Khrenova, Maria G.; Kulakova, A. M.; Nemukhin, Alexander V.

doi:10.1039/c8ob02262c

Cited by 14 publications

(15 citation statements)

References 56 publications

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“…In addition, Mroginski and coworkers also employed QM/MM simulations [29,30,31] and some recent publications based on this approach can be found in references [32,33,34,35,36,37]. Recently a QM/MM approach was also applied to investigate the covalent binding of the biliverdin (BV) chromophore to phytochrome domains [38] in the NIR FP miRFP670, which was also investigated experimentally [39,40,41]. On the other hand, excitation energies for tetrapyrrole chromophores found in phytochromes were calculated in the gas phase or in implicit solvent.…”

Section: Introductionmentioning

confidence: 99%

QM/MM Benchmarking of Cyanobacteriochrome Slr1393g3 Absorption Spectra

Wiebeler

Schapiro

2019

Molecules

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Cyanobacteriochromes are compact and spectrally diverse photoreceptor proteins that are promising candidates for biotechnological applications. Computational studies can contribute to an understanding at a molecular level of their wide spectral tuning and diversity. In this contribution, we benchmark methods to model a 110 nm shift in the UV/Vis absorption spectrum from a red- to a green-absorbing form of the cyanobacteriochrome Slr1393g3. Based on an assessment of semiempirical methods to describe the chromophore geometries of both forms in vacuo, we find that DFTB2+D leads to structures that are the closest to the reference method. The benchmark of the excited state calculations is based on snapshots from quantum mechanics/molecular mechanics molecular dynamics simulations. In our case, the methods RI-ADC(2) and sTD-DFT based on CAM-B3LYP ground state calculations perform the best, whereas no functional can be recommended to simulate the absorption spectra of both forms with time-dependent density functional theory. Furthermore, the difference in absorption for the lowest energy absorption maxima of both forms can already be modelled with optimized structures, but sampling is required to improve the shape of the absorption bands of both forms, in particular for the second band. This benchmark study can guide further computational studies, as it assesses essential components of a protocol to model the spectral tuning of both cyanobacteriochromes and the related phytochromes.

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Section: Introductionmentioning

confidence: 99%

QM/MM Benchmarking of Cyanobacteriochrome Slr1393g3 Absorption Spectra

Wiebeler

Schapiro

2019

Molecules

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“…In bacterial phytochromes, a covalent linkage is formed between the sulfur atom of the Cys residue in the PAS domain and the C3 2 atom of the A-ring vinyl moiety of the BV cofactor (Figure 4) [46]. An analysis of the interaction of BV with miRFP670 by molecular dynamics methods confirmed the C3 2 of the A-ring vinyl moiety of the cofactor as the most likely candidate for nucleophilic attack by the sulfur atom of the Cys residue from the N-terminal extension of the PAS domain [47]. The PCB cofactor contains ethylidene side chain at the A-ring with double bond between the C3 1 and C3 atoms as opposed to the BV cofactor with vinyl side chain (Figure 4).…”

Section: Resultsmentioning

confidence: 99%

Near-Infrared Markers based on Bacterial Phytochromes with Phycocyanobilin as a Chromophore

Stepanenko

Shpironok

et al. 2019

IJMS

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Biomarkers engineered on the basis of bacterial phytochromes with biliverdin IXα (BV) cofactor as a chromophore are increasingly used in cell biology and biomedicine, since their absorption and fluorescence spectra lie within the so-called optical “transparency window” of biological tissues. However, the quantum yield of BV fluorescence in these biomarkers does not exceed 0.145. The task of generating biomarkers with a higher fluorescence quantum yield remains relevant. To address the problem, we proposed the use of phycocyanobilin (PCB) as a chromophore of biomarkers derived from bacterial phytochromes. In this work, we characterized the complexes of iRFP713 evolved from RpBphP2 and its mutant variants with different location of cysteine residues capable of covalent tetrapyrrole attachment with the PCB cofactor. All analyzed proteins assembled with PCB were shown to have a higher fluorescence quantum yield than the proteins assembled with BV. The iRFP713/V256C and iRFP713/C15S/V256C assembled with PCB have a particularly high quantum yield of 0.5 and 0.45, which exceeds the quantum yield of all currently available near-infrared biomarkers. Moreover, PCB has 4 times greater affinity for iRFP713/V256C and iRFP713/C15S/V256C proteins compared to BV. These data establish iRFP713/V256C and iRFP713/C15S/V256C assembled with the PCB chromophore as promising biomarkers for application in vivo. The analysis of the spectral properties of the tested biomarkers allowed for suggesting that the high-fluorescence quantum yield of the PCB chromophore can be attributed to the lower mobility of the D-ring of PCB compared to BV.

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“…In a similar fashion, a full cycle of chemical transformations in the chromophore maturation in the wild‐type GFP (58) as well as reactions of the photo‐induced decomposition of the GFP chromophore upon photobleaching of the protein is considered (59). Also, we can describe the competing reactions of covalent binding of the biliverdin chromophore to cysteine residues in the bacterial phytochrome domains upon assembly a prospective variant of the near‐infrared fluorescent protein miRFP670 (60).…”

Section: Application Of Multiscale Methods To Photoactive Proteinsmentioning

confidence: 99%

Frontiers in Multiscale Modeling of Photoreceptor Proteins

Mroginski

Adam

Amoyal

et al. 2021

Photochem & Photobiology

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This perspective article highlights the challenges in the theoretical description of photoreceptor proteins using multiscale modeling, as discussed at the CECAM workshop in Tel Aviv, Israel. The participants have identified grand challenges and discussed the development of new tools to address them. Recent progress in understanding representative proteins such as green fluorescent protein, photoactive yellow protein, phytochrome, and rhodopsin is presented, along with methodological developments.

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Competition between two cysteines in covalent binding of biliverdin to phytochrome domains

Abstract: In this work, we disclose a mechanism of competing chemical reactions of protein assembly for a bacterial phytochrome using modern methods of molecular modeling.

Cited by 14 publications

References 56 publications

QM/MM Benchmarking of Cyanobacteriochrome Slr1393g3 Absorption Spectra

QM/MM Benchmarking of Cyanobacteriochrome Slr1393g3 Absorption Spectra

Near-Infrared Markers based on Bacterial Phytochromes with Phycocyanobilin as a Chromophore

Frontiers in Multiscale Modeling of Photoreceptor Proteins

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