Could tyrosine and tryptophan serve multiple roles in biological redox processes?

Abstract

Single-step electron tunnelling reactions can transport charges over distances of 15–20 Åin proteins. Longer-range transfer requires multi-step tunnelling processes along redox chains, often referred to as hopping. Long-range hopping via oxidized radicals of tryptophan and tyrosine, which has been identified in several natural enzymes, has been demonstrated in artificial constructs of the blue copper protein azurin. Tryptophan and tyrosine serve as hopping way stations in high-potential charge transport processes. It may be no coincidence that these two residues occur with greater-than-average frequency in O 2 - and H 2 O 2 -reactive enzymes. We suggest that appropriately placed tyrosine and/or tryptophan residues prevent damage from high-potential reactive intermediates by reduction followed by transfer of the oxidizing equivalent to less harmful sites or out of the protein altogether.

Challenges in engineering conductive protein fibres: Disentangling the knowledge

“…[69,70] In such cases, aromatic amino acids such as tyrosine, tryptophan, and phenylalanine can serve as sites for electron localization and act as relay stations for electrons moving between donor and acceptor species. [71][72][73][74] Based on this knowledge, an alternative conduction pathway has been proposed in G. sulfurreducens pili, where aromatic amino acids contribute to conduction not via electron delocalization but by acting as charge localization centres themselves. [47,48,75,76] Recently published work reveals more complex interactions could be at play; thin films of G. sulfurreducens protein fibres have been shown to generate current when a water concentration gradient is present in the film.…”

Hole hopping through tyrosine/tryptophan chains protects proteins from oxidative damage

“…Electron transfer rate constants for individual reaction steps (k ET ) were calculated according to Eq. 1 (where ΔG°is the standard free energy change for the electron transfer reaction and R is the gas constant) (5)(6)(7)(8). Reorganization energies (λ) for all reaction steps were set equal to 0.8 eV, the exponential distance decay parameter (β) was taken to be 1.1 Å -1 , the temperature (T) was taken to be 295 K, and the contact distance (r o ) was taken to be 3 Å. Distances (r) were defined as described in the main text, except for hemes where distances were defined to be to the Fe center.…”

“…The sulfur-containing amino acids (Met and Cys) can undergo reversible changes in response to ROS and RNS, whereas the oxidative reactions of other susceptible residues (Trp and Tyr) and the protein backbone are generally considered to be irreversible (4). The redox proteome also may provide protection from high-potential reactive intermediates formed during unsuccessful turnover in O 2 -using enzymes (5,6).…”

The Rise of Radicals in Bioinorganic Chemistry

“…[2] We began a search of structural databases that led to the discovery of long chains of tyrosines and tryptophans in several classes of proteins, most notably in metalloenzymes that utilize oxygen for redox function. [3] We further argued that these chains protect enzymes from oxidative destruction by steering highly oxidizing holes to regions where they can be rendered harmless by available reducing agents.…”