Theoretical study of proton coupled electron transfer reaction in the light state of the AppA BLUF photoreceptor

Abstract

The BLUF (blue light sensor using flavin adenine dinucleotide) domain is widely studied as a prototype for proton coupled electron transfer (PCET) reactions in biological systems. In this work, the photo-induced concerted PCET reaction from the light state of the AppA BLUF domain is investigated. To model the simultaneous transfer of two protons in the reaction, twodimensional potential energy surfaces for the double proton transfer are first calculated for the locally excited and charge transfer states, which are then used to obtain the vibrational wave function overlaps and the vibrational energy levels. Contributions to the PCET rate constant from each pair of vibronic states are then analyzed using the theory based on the Fermi's golden rule. We show that, the recently proposed light state structure of the BLUF domain with a tautomerized Gln63 residue is consistent with the concerted transfer of one electron and two protons. It is also found that, thermal fluctuations of the protein structure, especially the proton donor-acceptor distances, play an important role in determining the PCET reaction rate.

Intrinsic electronic conductivity of individual atomically resolved amyloid crystals reveals micrometer-long hole hopping via tyrosines

“…3B). PT rates are known to depend strongly on the proton donor-acceptor distances (44,48). Therefore, our analysis suggests that when the R1 conformation is stabilized by Zn 2+ , the Gln-O is the preferred proton acceptor in X1, whereas when the R1 conformation is not stabilized both the Gln-O and N are equally accessible.…”

“…Notably, in both X1 and X2, tyrosine is within close hydrogen bonding distance to the nearest glutamine side chain, positioning the glutamine as a probable proton acceptor for proton transfer (PT) (45). The tyrosine OH could be stabilized in a stretched configuration by hydrogen bonding interactions with the amide oxygen or nitrogen of the glutamine, analogously to the PT mechanism from Tyr to Gln proposed for the blue light using FAD (BLUF) domain protein (46)(47)(48).…”

Electron-Coupled Double Proton Transfer in the Slr1694 BLUF Photoreceptor: A Multireference Electronic Structure Study

“…Recently, another paper reported potential energy surfaces along two proton coordinates for the AppA BLUF photoreceptor protein. This recent work differs from the present work in several key aspects.…”

“…First, ref studied the AppA BLUF photoreceptor, rather than the Slr1694 BLUF photoreceptor, and experimental studies have identified significant differences in the photocycles of these two systems. ,, Second, a tautomerized and rotated Gln residue was used in ref as the starting geometry for double proton transfer. As a result, ref studied a different double proton transfer reaction, in which the Gln was rotated so the proton transferred from Tyr to the nitrogen of Gln and then from the oxygen of Gln to the flavin. The possibility of a keto–enol tautomerization of the Gln has been hypothesized in the literature for AppA BLUF, but evidence for Slr1694 tautomerization is lacking.…”

Applications of Proton-Coupled Electron Transfer in Organic Synthesis

“…Compared with the blooming publications on the organic synthetic methodologies promoted by PCET, the professional and deep experimental studies on PCET mechanism for revealing its fundamental rules are relatively rare in China, [151,[172][173][174][175] however, we are glad to see that more publications on theoretical studies have been published from Chinese groups in last five year. [173][174][175][176][177][178][179][180] Further explorations of PCET mechanism including how substrates and reaction conditions influence and regulate the PCET pathways, and so on, may provide novel ideas and methods for current synthetic methodology, and even help chemists discover unexpected patterns of chemical bond forming and breaking. Therefore, future works are supposed to focus on not only the synthetic applications, but also mechanism studies of PCET reactions, including new forms of PCET processes, which should benefit the development of other branches of chemistry.…”