Cryptochromes are flavoproteins playing different roles in variety of biological systems: they are involved in growth and development in plants, in the animal circadian clock, possess single-stranded DNA repair activity and are proposed as magnetoreceptors in migratory birds.1 Photoexcitation of the FAD cofactor initiates the cascade of electron transfer processes leading to the formation of the semi-reduced form of FAD. Tryptophan triad, three highly conserved Trp residues, is assumed to be the main electron transfer channel. However, recent experimental data on cryptochromes of the flowering plant Arabidopsis thaliana point to possible existence of alternative electron transfer pathways. In particular, involvement of cellular metabolites such as ATP and NAD in alternative electron transfer pathway have been demonstrated.2,3 Here we will present the results of computational studies of electron transfer pathways in two types of cryptochromes from Arabidopsis thaliana, cryptochromes 1 and 2. A new alternative electron transfer pathway is proposed that involves 3-step electron hopping from surface Y402 of cry1 (Y399 of cry2) to FAD via adenine of ATP and adenine of FAD. The efficiency of the competing conventional and the alternative electron transfer pathways is estimated based on computed free energy changes, reorganization energies, and electronic couplings. Classical MD simulations are performed to sample configurational space of the system, while the energetic parameters are extracted within QM/MM electronic embedding approach using density functional theory. Presented results contribute to understanding of complex electron transfer processes accompanying formation of photoactivated state of the protein in vivo and in vitro in diverse systems including cryptochromes in birds and humans. [1] Chaves I. et al. Annu. Rev. Plant Biol. 2011, 62, 335-364 [2] El-Esawi M. et al. Plant Signal. Behav. 2015, 10, 9 [3] Engelhard C. et al. The Plant Cell. 2014, 26, 4519–4531

Unraveling electron transfer pathways in cryptochromes

251st National Meeting (2016)

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