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

Area of Science:

• Biophysics
• Biochemistry
• Computational Chemistry

Background:

• Protein interfaces play crucial roles in biological electron transfer.
• Tryptophan residues are key players in mediating electron transfer within proteins.

Purpose of the Study:

• Investigate the role of a tryptophan quadruplex in mediating electron hole transfer (HT) at a protein-protein interface.
• Characterize the intermediates and pathways of HT in a dimeric azurin construct.

Main Methods:

• Molecular mechanics/molecular dynamics (MM/MD) and quantum mechanics/molecular mechanics/molecular dynamics (QM/MM/MD) simulations.
• Analysis of indole-indole distances, electronic couplings, and electrostatic potentials.
• Protein Data Bank (PDB) search for similar structural motifs.

Main Results:

• The tryptophan quadruplex mediates 8-11 ns intramolecular and interfacial HT after photooxidation.
• Simulations identified four distinct oxidized states with charge localized on individual tryptophan indoles.
• Interfacial electron transfer is kinetically and energetically favored over intramolecular transfer.
• Solvating water molecules at the interface support electron transfer.

Conclusions:

• Tryptophan quadruplexes are important for mediating electron transfer at protein interfaces.
• The structural and dynamic features of the quadruplex and its solvation environment dictate transfer efficiency.
• Four-tryptophan clusters are common in oxidoreductases, suggesting a conserved functional motif.