Cu(I) recognition via cation-pi and methionine interactions in CusF

Nat Chem Biol. 2008 Feb;4(2):107-9. doi: 10.1038/nchembio.2007.57. Epub 2007 Dec 23.


Methionine-rich motifs have an important role in copper trafficking factors, including the CusF protein. Here we show that CusF uses a new metal recognition site wherein Cu(I) is tetragonally displaced from a Met2His ligand plane toward a conserved tryptophan. Spectroscopic studies demonstrate that both thioether ligation and strong cation-pi interactions with tryptophan stabilize metal binding. This novel active site chemistry affords mechanisms for control of adventitious metal redox and substitution chemistry.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cation Transport Proteins / chemistry*
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / metabolism*
  • Cations / chemistry
  • Cations / metabolism
  • Copper / chemistry
  • Copper / metabolism*
  • Copper Transport Proteins
  • Escherichia coli Proteins
  • Methionine / genetics
  • Methionine / metabolism*
  • Models, Molecular
  • Protein Binding
  • Protein Structure, Tertiary


  • Cation Transport Proteins
  • Cations
  • Copper Transport Proteins
  • CusF protein, E coli
  • Escherichia coli Proteins
  • Copper
  • Methionine