Reduction potential tuning at a type 1 copper site does not compromise electron transfer reactivity

J Am Chem Soc. 2005 Nov 30;127(47):16453-9. doi: 10.1021/ja054426v.


Type 1 (T1) copper sites promote biological electron transfer (ET) and typically possess a weakly coordinated thioether sulfur from an axial Met [Cu(II)-Sdelta approximately 2.6 to 3.3 A] along with the conserved His2Cys equatorial ligands. A strong axial bond [Cu(II)-Oepsilon1 approximately 2.2 A] is sometimes provided by a Gln (as in the stellacyanins), and the axial ligand can be absent (a Val, Leu or Phe in the axial position) as in ceruloplasmin, Fet3p, fungal laccases and some plantacyanins (PLTs). Cucumber basic protein (CBP) is a PLT which has a relatively short Cu(II)-S(Met89) axial bond (2.6 A). The Met89Gln variant of CBP has an electron self-exchange (ESE) rate constant (k(ese), a measure of intrinsic ET reactivity) approximately 7 times lower than that of the wild-type protein. The Met89Val mutation to CBP results in a 2-fold increase in k(ese). As the axial interaction decreases from strong Oepsilon1 of Gln to relatively weak Sdelta of Met to no ligand (Val), ESE reactivity is therefore enhanced by approximately 1 order of magnitude while the reduction potential increases by approximately 350 mV. The variable coordination position at this ubiquitous ET site provides a mechanism for tuning the driving force to optimize ET with the correct partner without significantly compromising intrinsic reactivity. The enhanced reactivity of a three-coordinate T1 copper site will facilitate intramolecular ET in fungal laccases and Fet3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Azurin / chemistry
  • Binding Sites
  • Copper / chemistry*
  • Electron Transport
  • Magnetic Resonance Spectroscopy
  • Metalloproteins / chemistry
  • Models, Molecular
  • Molecular Structure
  • Oxidation-Reduction
  • Plant Proteins* / chemistry


  • Metalloproteins
  • Plant Proteins
  • cupredoxin
  • Azurin
  • CBP protein, Cucumis sativus
  • Copper