@article{5bc78b4df6ab4eb5abc4d9ecbf18a446,
title = "Design of a single protein that spans the entire 2-V range of physiological redox potentials",
abstract = "The reduction potential (E°′) is a critical parameter in determining the efficiency of most biological and chemical reactions. Biology employs three classes of metalloproteins to cover the majority of the 2-V range of physiological E°′s. An ultimate test of our understanding of E°′ is to find out the minimal number of proteins and their variants that can cover this entire range and the structural features responsible for the extreme E°′. We report herein the design of the protein azurin to cover a range from +970 mV to -954 mV vs. standard hydrogen electrode (SHE) by mutating only five residues and using two metal ions. Spectroscopic methods have revealed geometric parameters important for the high E°′. The knowledge gained and the resulting water-soluble redox agents with predictable E°′s, in the same scaffold with the same surface properties, will find wide applications in chemical, biochemical, biophysical, and biotechnological fields.",
keywords = "Azurin, Cupredoxins, Electron transfer, Reduction potential, Secondary coordination sphere",
author = "Parisa Hosseinzadeh and Marshall, {Nicholas M.} and Chac{\'o}n, {Kelly N.} and Yang Yu and Nilges, {Mark J.} and New, {Siu Yee} and Tashkov, {Stoyan A.} and Blackburn, {Ninian J.} and Yi Lu",
note = "Funding Information: We thank Mr. Kevin Harnden for help with protein purification, Dr. Zhou Dai for initial EXAFS data collection, Dr. Rodney Burton for initial help in freeze-quench EPR in early time points, Mr. Bryant Kearl for collecting preliminary CV data, Mr. Khosro Khosravi for revising Fig. 1, and Mr. Shiliang Tian for discussions and comments. This material is based on work supported by the US National Science Foundation under Award CHE 14-13328 (to Y.L.) and US National Institutes of Health under Award NIH R01GM054803 (to N.J.B). K.N.C. was supported by National Science Foundation Graduate Research Fellowship DGE-0925180. We acknowledge the use of facilities at the Stanford Synchrotron Radiation Lightsource (SSRL), supported by the US Department of Energy (DOE), Office of Science, Office of Basic Energy Sciences under Contract DE-AC02-76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research, the National Institutes of Health, and by the National Institute of General Medical Sciences (including P41GM103393).",
year = "2016",
month = jan,
day = "12",
doi = "10.1073/pnas.1515897112",
language = "English (US)",
volume = "113",
pages = "262--267",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "2",
}