Design of a single protein that spans the entire 2-V range of physiological redox potentials

Parisa Hosseinzadeh, Nicholas M. Marshall, Kelly N. Chacón, Yang Yu, Mark J. Nilges, Siu Yee New, Stoyan A. Tashkov, Ninian Blackburn, Yi Lu

Research output: Contribution to journalArticle

41 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)262-267
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number2
StatePublished - Jan 12 2016



  • Azurin
  • Cupredoxins
  • Electron transfer
  • Reduction potential
  • Secondary coordination sphere

ASJC Scopus subject areas

  • General

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