# Electron Transport through a Tryptophan Quadruplex in a Dimeric Azurin Construct

## TL;DR

This paper shows how a cluster of four tryptophan molecules in a dimeric azurin protein helps transfer electrons quickly between protein subunits.

## Contribution

The study reveals that a tryptophan quadruplex enables efficient interfacial electron transfer through specific structural and solvation features.

## Key findings

- The tryptophan quadruplex exists in four distinct oxidized states with localized charges.
- Interfacial electron transfer is faster and more energetically favorable than intramolecular transfer.
- Water molecules solvating the indoles facilitate electron transfer by shifting slightly toward charged regions.

## Abstract

A tryptophan quadruplex at a protein–protein interface
in
a dimeric azurin construct mediates 8–11 ns intramolecular
as well as interfacial electron hole transfer (HT) triggered by ultrafast
photooxidation by a covalently attached organometallic chromophore
(Takematsu et al. J. Phys. Chem. B., 2019, 123, 1578–1591).
MM/MD and QM/MM/MD simulations characterized intermediates of through-quadruplex
HT (i.e., states with one of the tryptophans oxidized) and assessed
the feasibility of individual HT pathways. Simulations demonstrated
that the oxidized quadruplex in aqueous solution occurs in four distinct
states where the charge is predominantly (≥90%) localized at
individual tryptophan indoles. Distributions of indole–indole
distances, electronic couplings, as well as electrostatic potentials
at indoles indicate kinetic and energetic preferences of interfacial
over intramolecular ET. Interfacial indoles are tightly solvated by
a chain of quasi-structural water molecules that are shielded from
bulk water by protein folds. Solvating water molecules support ET
by 0.1–0.2 Å shifts toward positively charged indoles.
PDB search revealed that 4-Trp clusters are rather common among naturally
occurring oxidoreductases.