PMID- 10221913
OWN - NLM
STAT- MEDLINE
DCOM- 19990520
LR  - 20190619
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 284
IP  - 5415
DP  - 1999 Apr 30
TI  - Undetectable intracellular free copper: the requirement of a copper chaperone for
      superoxide dismutase.
PG  - 805-8
AB  - 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.
FAU - Rae, T D
AU  - Rae TD
AD  - Department of Chemistry and Department of Biochemistry, Molecular Biology and
      Cell Biology, Northwestern University, Evanston, IL 60208, USA.
FAU - Schmidt, P J
AU  - Schmidt PJ
FAU - Pufahl, R A
AU  - Pufahl RA
FAU - Culotta, V C
AU  - Culotta VC
FAU - O'Halloran, T V
AU  - O'Halloran TV
LA  - eng
GR  - R01 GM054111/GM/NIGMS NIH HHS/United States
GR  - F32 GM19457/GM/NIGMS NIH HHS/United States
GR  - GM 50016/GM/NIGMS NIH HHS/United States
GR  - GM 54111/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Apoenzymes)
RN  - 0 (CCS1 protein, S cerevisiae)
RN  - 0 (Chelating Agents)
RN  - 0 (Fungal Proteins)
RN  - 0 (Molecular Chaperones)
RN  - 0 (Phenanthrolines)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 73348-75-1 (bathocuproine sulfonate)
RN  - 789U1901C5 (Copper)
RN  - 9038-94-2 (Metallothionein)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
SB  - IM
CIN - Science. 1999 Apr 30;284(5415):748-9. PMID: 10336397
MH  - Apoenzymes/metabolism
MH  - Chelating Agents/pharmacology
MH  - Copper/*metabolism
MH  - Cytoplasm/metabolism
MH  - Enzyme Activation
MH  - Fungal Proteins/isolation & purification/metabolism
MH  - Metallothionein/physiology
MH  - Molecular Chaperones/isolation & purification/*metabolism
MH  - Phenanthrolines/pharmacology
MH  - Recombinant Proteins/isolation & purification/metabolism
MH  - Saccharomyces cerevisiae/*metabolism
MH  - *Saccharomyces cerevisiae Proteins
MH  - Superoxide Dismutase/*metabolism
EDAT- 1999/04/30 00:00
MHDA- 1999/04/30 00:01
CRDT- 1999/04/30 00:00
PHST- 1999/04/30 00:00 [pubmed]
PHST- 1999/04/30 00:01 [medline]
PHST- 1999/04/30 00:00 [entrez]
AID - 10.1126/science.284.5415.805 [doi]
PST - ppublish
SO  - Science. 1999 Apr 30;284(5415):805-8. doi: 10.1126/science.284.5415.805.