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Cited by 1,629

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Undetectable Intracellular Free Copper: The Requirement of a Copper Chaperone for Superoxide Dismutase

Rae, T. D., Schmidt, P. J., Pufahl, R. A., Culotta, V. C., V. O'Halloran, T.·1999·Science

Abstract

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 μM in yeast) and copper (70 μM 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.

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Metadata

Authors
Rae, T. D., Schmidt, P. J., Pufahl, R. A., Culotta, V. C., & V. O'Halloran, T.
Venue
Science
Published
1999-04-30
Volume
284
Issue
5415
Pages
805-808
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W1963874808
Cited by
1,629
References
1
FWCI
54.79
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: Undetectable Intracellular Free Copper: The Requirement of a Copper Chaperone for Superoxide Dismutase. https://app.cochat.ai/papers/10.1126/science.284.5415.805
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Rae, T. D., Schmidt, P. J., Pufahl, R. A., Culotta, V. C., & V. O'Halloran, T. (1999). Undetectable Intracellular Free Copper: The Requirement of a Copper Chaperone for Superoxide Dismutase. Science. https://doi.org/10.1126/science.284.5415.805

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