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 J. Blackburn, Yi Lu

Research output: Contribution to journalArticlepeer-review


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


Dive into the research topics of 'Design of a single protein that spans the entire 2-V range of physiological redox potentials'. Together they form a unique fingerprint.

Cite this