Wide-dynamic-range kinetic investigations of deep proton tunnelling in proteins

Abstract

Abstract:Directional proton transport along "wires" that feed biochemical reactions in proteins is poorly understood. Amino acid residues with high pK a are seldom considered as active transport elements in such wires because of their large classical barrier for proton dissociation. Here we use the light-triggered proton wire of the green fluorescent protein (GFP) to study its ground electronic state proton transport kinetics, revealing a large temperature-dependent kinetic isotope effect. We show that "deep" proton tunneling between hydrogen-bonded oxygen atoms having a typical donor-acceptor distance of 2.7-2.8 Ǻ fully accounts for the rates at all temperatures, including the unexpectedly large value (2.5 10 9 s -1 ) found at room temperature. The rate limiting step in GFP is assigned to tunneling of the ionization-resistant serine hydroxyl proton. This suggests how high pK a residues within a proton wire can act as a "tunnel-diode" to kinetically trap protons and control the direction of proton flow.

Multiscale modelization in a small virus: Mechanism of proton channeling and its role in triggering capsid disassembly

“…Computational investigations and several experimental approaches have focused on different aspects of water-mediated proton transfer in biological systems. Some examples are the gramicidin A transmembrane channel [ 51 – 53 ], bacteriorhodopsin [ 54 – 56 ], cytochrome C oxidase [ 57 , 58 ], influenza AM2 proton channel [ 59 ], green fluorescent protein (GFP) [ 60 ], the voltage-gated proton channel HV1 [ 61 ], carbonic anhydrase [ 62 ] and so-called bioprotonic devices [ 63 ].…”

Two-Dimensional Impulsively Stimulated Resonant Raman Spectroscopy of Molecular Excited States

“…We note that the correct identification of the origin of all the off-diagonal peaks-and, in particular, the assignment of peaks involving the overtone of the 1147 cm −1 -is required to prevent wrong interpretations of the spectra; more importantly, it demonstrates the sensitivity of this technique to the Duschinsky mixing. Since the Duschinsky rotation affects the relative weights between vibronic transitions, mode mixing has a large impact on the kinetics and efficiency of charge transfer processes [70][71][72], making 2D-ISRS particularly suitable for studying this class of samples.…”

Deciphering the selectivity of inhibitor MKC9989 towards residue K907 in IRE1α; a multiscalein silicoapproach

“…(2) It is well-known that, due to light weight of the proton, quantum effects cannot be neglected for reactions involving proton transfer. 49 Proton tunneling is a quantum mechanical phenomenon that can justify how protons can transfer from one microstate to another one by passing through the energy barrier between the two. 49 The contour map prole of the PES (Fig.…”