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Undetectable intracellular free copper: the requirement of a copper chaperone for superoxide dismutase.

The copper chaperone for the superoxide dismutase (CCS) gene is necessary for expression of an active, copper-bound form of superoxide dismutase (SOD1) in vivo in spite of the high affinity of SOD1 for copper (dissociation constant = 6 fM) and the high intracellular concentrations of both SOD1 (10 microM in yeast) and copper (70 microM in yeast). In vitro studies demonstrated that purified Cu(I)-yCCS protein is sufficient for direct copper activation of apo-ySOD1 but is necessary only when the concentration of free copper ions ([Cu]free) is strictly limited. Moreover, the physiological requirement for yCCS in vivo was readily bypassed by elevated copper concentrations and abrogation of intracellular copper-scavenging systems such as the metallothioneins. This metallochaperone protein activates the target enzyme through direct insertion of the copper cofactor and apparently functions to protect the metal ion from binding to intracellular copper scavengers. These results indicate that intracellular [Cu]free is limited to less than one free copper ion per cell and suggest that a pool of free copper ions is not used in physiological activation of metalloenzymes.

Pubmed ID: 10221913


  • Rae TD
  • Schmidt PJ
  • Pufahl RA
  • Culotta VC
  • O'Halloran TV


Science (New York, N.Y.)

Publication Data

April 30, 1999

Associated Grants

  • Agency: NIGMS NIH HHS, Id: F32 GM19457
  • Agency: NIGMS NIH HHS, Id: GM 50016
  • Agency: NIGMS NIH HHS, Id: GM 54111
  • Agency: NIGMS NIH HHS, Id: R01 GM054111

Mesh Terms

  • Apoenzymes
  • Chelating Agents
  • Copper
  • Cytoplasm
  • Enzyme Activation
  • Fungal Proteins
  • Metallothionein
  • Molecular Chaperones
  • Phenanthrolines
  • Recombinant Proteins
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Superoxide Dismutase