Short-Range Electron Transfer in Reduced Flavodoxin: Ultrafast Nonequilibrium Dynamics Coupled with Protein Fluctuations

Abstract

Short-range electron transfer (ET) in proteins is an ultrafast process on the similar time scales as local protein-solvent fluctuation, and thus the two dynamics are coupled. Here we use semiquinone flavodoxin and systematically characterized the photoinduced redox cycle with 11 mutations of different aromatic electron donors (tryptophan and tyrosine) and local residues to change redox properties. We observed the forward and backward ET dynamics in a few picoseconds, strongly following a stretched behavior resulting from a coupling between local environment relaxations and these ET processes. We further observed the hot vibrational-state formation through charge recombination and the subsequent cooling dynamics also in a few picoseconds. Combined with the ET studies in oxidized flavodoxin, these results coherently reveal the evolution of the ET dynamics from single to stretched exponential behaviors and thus elucidate critical time scales for the coupling. The observed hot vibration-state formation is robust and should be considered in all photoinduced back ET processes in flavoproteins.

Short‐Lived Radical Intermediates in the Photochemistry of Glucose Oxidase

“…This timescale is beyond the typical timescale of vibrational cooling in proteins. This lends further support to the idea that the spectral feature reflects a true intermediate, and not a spectral relaxation of the flavin as recently suggested …”

“…This lends further support to the idea that the spectral feature reflects a true intermediate, and not a spectral relaxation of the flavin as recently suggested. [33] The role of individual residues in the charge transfer processes in GOX could not be inferred from the complex data and will require additional experiments associating site-directed mutagenesis and spectroscopy.…”

Characterization of Light-Induced, Short-Lived Interacting Radicals in the Active Site of Flavoprotein Ferredoxin-NADP+ Oxidoreductase

“…For instance, in proteins bearing flavin as a cofactor, flavin photoreduction by ET from nearby tyrosine (TyrOH) or tryptophan (TrpH) to excited flavin is an efficient fluorescence quenching pathway. [7][8][9][10][11][12][13] Such pathways are operational in several light-sensitive biological functions, as demonstrated by studies of DNA photolyase, 14,15 cryptochrome 12 and BLUF domain proteins. 17,18 Yet, flavin photoreduction can also occur in the vast majority of flavoproteins that are not functionally light-active.…”

Tuning Proton Transfer Thermodynamics in SARS-Cov-2 Main Protease: Implications for Catalysis and Inhibitor Design

“…This is a very relevant point in charge transfer processes, which have been shown to strongly depend on the structural fluctuations of the environment. 22,23 More details on the MD-PMM approach can be found in the Supporting Information (SI).…”