Protein control of photochemistry and transient intermediates in phytochromes

Abstract

Phytochromes are ubiquitous photoreceptors responsible for sensing light in plants, fungi and bacteria. Their photoactivation is initiated by the photoisomerization of the embedded bilin chromophore, which triggers a large conformational change in the protein. The initial photoisomerization and the following structural changes propagating from the chromophore to the entire protein are controlled by a delicate interplay of interactions between the chromophore and the protein residues. Although the numerous studies, the molecular details of this control remain elusive. Here, we apply an integrated computational approach that combines non-adiabatic and adiabatic molecular dynamics simulations to the Deinococcus radiodurans bacteriophytochrome. Our simulations show that the photoisomerization of the chromophore proceeds through a hula-twist mechanism whose kinetics is mainly determined by the hydrogen-bonding interaction of the chromophore with a close-by histidine. The resulting photoproduct rapidly relaxes in an early intermediate thanks to a stabilizing effect of a tyrosine, and finally evolves into a late intermediate, characterized by a more disordered binding pocket and a weakening of the aspartate-to-arginine salt-bridge interaction, whose cleavage is essential to interconvert the phytochrome to the final active state.

Photoisomerization of phytochrome chromophore models: An XMS-CASPT2 study

“…This preference has also been reported in QM/MM studies of various phytochromes. 20,22,32,33 This work can serve as a guide for future experimental and computational studies on the excited state dynamics of truncated tetrapyrroles. In addition, the study can also serve as a reference in benchmarks of computational methods since the current study demonstrates that the XMS-CASPT2 method can effectively describe CIs in these systems.…”

“…18 Such an active space size is computationally intractable since the maximum size currently achievable is 18 electrons in 18 orbitals. 19 Therefore, in previous studies a compromise was chosen to either employ approximate electronic structure methods, such as a semi-empirical method, [20][21][22] or to truncate the chromophore. [23][24][25][26][27][28] In the latter approach, typically, the propionic acid groups 23 are replaced by hydrogen atoms because they are not part of the conjugated π-system.…”

“…This is consistent with the recent QM/MM non-adiabatic molecular dynamics (NAMD) study by Groenhof and coworkers 33 with SA2-CASSCF/3-21G as the QM level of theory on the Deinococcus radiodurans phytochrome. For the same phytochrome, Mennucci and coworkers 22 carried out non-adiabatic molecular dynamics. They observed a concerted rotation of a single and double bond, which is known as a hula-twist isomerization mechanism.…”

The impact of different geometrical restrictions on the nonadiabatic photoisomerization of biliverdin chromophores

“…24–27 In theory, QM/MM studies for BV and PCB suggest that photoisomerization occurs at the C 15 C 16 bond. 28–31 Differently, Ulijasz et al proposed that the twist of the C 4 C 5 double bond is the key to the isomerization of PCB. 23 At the same time, some studies also pointed out that the rotation of the C 10 C 11 double bond was noticeable in the BV and PΦB isomerization, 32–34 at least in the gas phase.…”