Frustration Dynamics and Electron-Transfer Reorganization Energies in Wild-Type and Mutant Azurins
Journal article, 2022

Long-range electron tunneling through metalloproteins is facilitated by evolutionary tuning of donor-acceptor electronic couplings, formal electrochemical potentials, and active-site reorganization energies. Although the minimal frustration of the folding landscape enables this tuning, residual frustration in the vicinity of the metallocofactor can allow conformational fluctuations required for protein function. We show here that the constrained copper site in wild-type azurin is governed by an intricate pattern of minimally frustrated local and distant interactions that together enable rapid electron flow to and from the protein. In contrast, sluggish electron transfer reactions (unfavorable reorganization energies) of active-site azurin variants are attributable to increased frustration near to as well as distant from the copper site, along with an exaggerated oxidation-state dependence of both minimally and highly frustrated interaction patterns.


Xun Chen

Rice University

Mingchen Chen

Rice University

Peter G. Wolynes

Rice University

Pernilla Wittung Stafshede

Chalmers, Biology and Biological Engineering, Chemical Biology

Harry B. Gray

California Institute of Technology (Caltech)

Journal of the American Chemical Society

0002-7863 (ISSN) 1520-5126 (eISSN)

Vol. 144 9 4178-4185

Subject Categories

Biochemistry and Molecular Biology

Theoretical Chemistry

Biocatalysis and Enzyme Technology





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Latest update

3/9/2022 8