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Coordination chemistry of copper proteins: how nature handles a toxic cargo for essential function.

Publication ,  Journal Article
Rubino, JT; Franz, KJ
Published in: Journal of inorganic biochemistry
February 2012

Biological copper is coordinated predominantly by just three ligand types: the side chains of histidine, cysteine, and methionine, with of course some exceptions. The arrangement of these components, however, is fascinating. The diversity provided by just these three ligands provides choices of nitrogen vs. sulfur, neutral vs. charged, hydrophilic vs. hydrophobic, susceptibility to oxidation, and degree of pH-sensitivity. In this review we examine how the total number of ligands, their spatial arrangement and solvent accessibility, the various combinations of imidazole, thiolate, and thioether donors, all work together to provide binding sites that either enable copper to carry out a function, or safely transport it in a way that prevents toxic reactivity. We separate copper proteins into two broad classes, those that utilize the metal as a cofactor, or those that traffic the metal. Enzymes and proteins that utilize copper as a cofactor use high affinity sites of high coordination numbers of 4-5 that prevent loss of the metal during redox cycling. Copper trafficking proteins, on the other hand, promote metal transfer either by having low affinity binding sites with moderate coordination number ~4, or by having lower coordinate binding sites of 2-3 ligands that bind with high affinity. Both strategies retain the metal but allow transfer under appropriate conditions. Analysis of studies from our own lab on model peptides, combined with those from other labs, raises an interesting hypothesis that various methionine/histidine/cysteine combinations provide organisms with dynamic, multifunctional domains on copper trafficking proteins that facilitate copper transfer under different extracellular, subcellular, and tissue-specific scenarios of pH, redox environment, and presence of other copper carriers or target proteins.

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Published In

Journal of inorganic biochemistry

DOI

EISSN

1873-3344

ISSN

0162-0134

Publication Date

February 2012

Volume

107

Issue

1

Start / End Page

129 / 143

Related Subject Headings

  • Protein Binding
  • Oxidation-Reduction
  • Metalloproteins
  • Inorganic & Nuclear Chemistry
  • Humans
  • Copper
  • Coordination Complexes
  • Binding Sites
  • Animals
  • Amino Acid Motifs
 

Citation

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Rubino, J. T., & Franz, K. J. (2012). Coordination chemistry of copper proteins: how nature handles a toxic cargo for essential function. Journal of Inorganic Biochemistry, 107(1), 129–143. https://doi.org/10.1016/j.jinorgbio.2011.11.024
Rubino, Jeffrey T., and Katherine J. Franz. “Coordination chemistry of copper proteins: how nature handles a toxic cargo for essential function.Journal of Inorganic Biochemistry 107, no. 1 (February 2012): 129–43. https://doi.org/10.1016/j.jinorgbio.2011.11.024.
Rubino JT, Franz KJ. Coordination chemistry of copper proteins: how nature handles a toxic cargo for essential function. Journal of inorganic biochemistry. 2012 Feb;107(1):129–43.
Rubino, Jeffrey T., and Katherine J. Franz. “Coordination chemistry of copper proteins: how nature handles a toxic cargo for essential function.Journal of Inorganic Biochemistry, vol. 107, no. 1, Feb. 2012, pp. 129–43. Epmc, doi:10.1016/j.jinorgbio.2011.11.024.
Rubino JT, Franz KJ. Coordination chemistry of copper proteins: how nature handles a toxic cargo for essential function. Journal of inorganic biochemistry. 2012 Feb;107(1):129–143.
Journal cover image

Published In

Journal of inorganic biochemistry

DOI

EISSN

1873-3344

ISSN

0162-0134

Publication Date

February 2012

Volume

107

Issue

1

Start / End Page

129 / 143

Related Subject Headings

  • Protein Binding
  • Oxidation-Reduction
  • Metalloproteins
  • Inorganic & Nuclear Chemistry
  • Humans
  • Copper
  • Coordination Complexes
  • Binding Sites
  • Animals
  • Amino Acid Motifs