Experts and Doctors on copper in Salt Lake City, Utah, United States


Locale: Salt Lake City, Utah, United States
Topic: copper

Top Publications

  1. Fetherolf M, Boyd S, Taylor A, Kim H, Wohlschlegel J, Blackburn N, et al. Copper-zinc superoxide dismutase is activated through a sulfenic acid intermediate at a copper ion entry site. J Biol Chem. 2017;292:12025-12040 pubmed publisher
    ..Sod1 is the predominant disulfide bond-requiring enzyme in the cytoplasm, and this copper-induced mechanism of disulfide bond formation obviates the need for a thiol/disulfide oxidoreductase in that compartment. ..
  2. McMillin G, Travis J, Hunt J. Direct measurement of free copper in serum or plasma ultrafiltrate. Am J Clin Pathol. 2009;131:160-5 pubmed publisher
    ..Free copper concentrations for patients diagnosed with WD were at least 6-fold greater than the upper limit of the reference interval before treatment but fell within the reference interval after treatment. ..
  3. Yu W, Farrell R, Stillman D, Winge D. Identification of SLF1 as a new copper homeostasis gene involved in copper sulfide mineralization in Saccharomyces cerevisiae. Mol Cell Biol. 1996;16:2464-72 pubmed
    ..This process may coordinate with the Cup1 pathway at different copper concentrations to prevent copper-induced toxicity...
  4. Cobine P, Pierrel F, Leary S, Sasarman F, Horng Y, Shoubridge E, et al. The P174L mutation in human Sco1 severely compromises Cox17-dependent metallation but does not impair copper binding. J Biol Chem. 2006;281:12270-6 pubmed
    ..They further suggest that defective Cox17-mediated copper metallation of Sco1, as well as the subsequent failure of Cu(A) site maturation, is the basis for the inefficient assembly of the cytochrome c oxidase complex in SCO1 patients. ..
  5. Dameron C, Winge D, George G, Sansone M, Hu S, Hamer D. A copper-thiolate polynuclear cluster in the ACE1 transcription factor. Proc Natl Acad Sci U S A. 1991;88:6127-31 pubmed
    ..The Cu cluster organizes and stabilizes the conformation of the N-terminal domain of ACE1 for specific DNA binding. ..
  6. Rigby K, Cobine P, Khalimonchuk O, Winge D. Mapping the functional interaction of Sco1 and Cox2 in cytochrome oxidase biogenesis. J Biol Chem. 2008;283:15015-22 pubmed publisher
    ..In addition, the mutants failed to suppress the hydrogen peroxide sensitivity of sco1Delta cells. These studies implicate different surfaces on Sco1 for interaction or function with Cox17 and Cox2. ..
  7. Rigby K, Zhang L, Cobine P, George G, Winge D. characterization of the cytochrome c oxidase assembly factor Cox19 of Saccharomyces cerevisiae. J Biol Chem. 2007;282:10233-42 pubmed
    ..Cysteinyl residues important for Cu(I) binding are also shown to be important for the in vivo function of Cox19. Thus, a correlation exists in the ability to bind Cu(I) and in vivo function. ..
  8. Srinivasan C, Posewitz M, George G, Winge D. Characterization of the copper chaperone Cox17 of Saccharomyces cerevisiae. Biochemistry. 1998;37:7572-7 pubmed
    ..26 A, plus a short Cu-Cu distance of 2.7 A, indicating a binuclear cluster in Cox17. The cuprous-thiolate cluster in Cox17 is substantially more labile than structurally related clusters in metallothioneins. ..
  9. Jensen L, Posewitz M, Srinivasan C, Winge D. Mapping of the DNA binding domain of the copper-responsive transcription factor Mac1 from Saccharomyces cerevisiae. J Biol Chem. 1998;273:23805-11 pubmed
    ..The elements appear to function synergistically. Increasing the number of elements yields more than additive enhancements in CTR1 expression. ..

More Information


  1. Fleming A, Muller J, Ji I, Burrows C. Characterization of 2'-deoxyguanosine oxidation products observed in the Fenton-like system Cu(II)/H2O2/reductant in nucleoside and oligodeoxynucleotide contexts. Org Biomol Chem. 2011;9:3338-48 pubmed publisher
    ..Product distribution studies provide insight into the role of the reductant in partitioning of dG base oxidation along the C5 and C8 pathways. ..
  2. Wang L, Becker J, Wu Q, Oliveira M, Bozza F, Schwager A, et al. Bioimaging of copper alterations in the aging mouse brain by autoradiography, laser ablation inductively coupled plasma mass spectrometry and immunohistochemistry. Metallomics. 2010;2:348-53 pubmed publisher
    ..This study illustrates the importance of a multi-modality approach in studying the biodistribution and homeostasis of Cu in the brain. ..
  3. Schubert H, Rose R, Leech H, Brindley A, Hill C, Rigby S, et al. Structure and function of SirC from Bacillus megaterium: a metal-binding precorrin-2 dehydrogenase. Biochem J. 2008;415:257-63 pubmed publisher
  4. Keller G, Bird A, Winge D. Independent metalloregulation of Ace1 and Mac1 in Saccharomyces cerevisiae. Eukaryot Cell. 2005;4:1863-71 pubmed
    ..Likewise, high expression of a copper-binding, non-DNA-binding Mac1 mutant is without effect on the copper activation of Ace1. Thus, metalloregulation of Ace1 and Mac1 occurs independently. ..
  5. Carr H, George G, Winge D. Yeast Cox11, a protein essential for cytochrome c oxidase assembly, is a Cu(I)-binding protein. J Biol Chem. 2002;277:31237-42 pubmed
    ..Cytochrome c oxidase activity is reduced in these mutants. Thus, the residues important for Cu(I) binding correlate with in vivo function, suggesting that Cu(I) binding is important in Cox11 function. ..
  6. Heaton D, George G, Garrison G, Winge D. The mitochondrial copper metallochaperone Cox17 exists as an oligomeric, polycopper complex. Biochemistry. 2001;40:743-51 pubmed
    ..Thus, the oligomeric state of Cox17 may be important to its physiological function. ..
  7. Cobine P, Pierrel F, Bestwick M, Winge D. Mitochondrial matrix copper complex used in metallation of cytochrome oxidase and superoxide dismutase. J Biol Chem. 2006;281:36552-9 pubmed
    ..These data suggest that attenuation of the matrix CuL complex via heterologous competitors limits available copper for metallation of CcO and Sod1 within the IMS. The ligand also exists in the cytoplasm in an apparent metal-free state. ..
  8. Horng Y, Leary S, Cobine P, Young F, George G, Shoubridge E, et al. Human Sco1 and Sco2 function as copper-binding proteins. J Biol Chem. 2005;280:34113-22 pubmed
    ..Both the mutant yeast and human proteins were nonfunctional, suggesting the importance of this aspartate for normal function. Taken together, these data suggest that both Cu(I) and Cu(II) binding are critical for normal Sco function. ..
  9. Horng Y, Cobine P, Maxfield A, Carr H, Winge D. Specific copper transfer from the Cox17 metallochaperone to both Sco1 and Cox11 in the assembly of yeast cytochrome C oxidase. J Biol Chem. 2004;279:35334-40 pubmed
    ..Metallation of these domains was strictly dependent on the co-expression of Cox17. Thus, Cox17 represents a novel copper chaperone that delivers copper to two proteins. ..
  10. Nittis T, George G, Winge D. Yeast Sco1, a protein essential for cytochrome c oxidase function is a Cu(I)-binding protein. J Biol Chem. 2001;276:42520-6 pubmed
    ..Thus, the function of Sco1 correlates with Cu(I) binding. Data obtained from size-exclusion chromatography experiments with mitochondrial lysates suggest that full-length Sco1 may be oligomeric in vivo. ..
  11. Sandoval I, Manos E, Van Wagoner R, Delacruz R, Edes K, Winge D, et al. Juxtaposition of chemical and mutation-induced developmental defects in zebrafish reveal a copper-chelating activity for kalihinol F. Chem Biol. 2013;20:753-63 pubmed publisher
    ..Our data support this mechanism of action for kalihinol F and the utility of zebrafish as an effective system for identifying therapeutic and target pathways. ..
  12. Martins L, Jensen L, Simon J, Keller G, Winge D, Simons J. Metalloregulation of FRE1 and FRE2 homologs in Saccharomyces cerevisiae. J Biol Chem. 1998;273:23716-21 pubmed
    ..From the three Mac1-responsive elements in FRE7, a new consensus sequence for Mac1 binding can be established as TTTGC(T/G)C(A/G). ..
  13. Keller G, Ray E, Brown P, Winge D. Haa1, a protein homologous to the copper-regulated transcription factor Ace1, is a novel transcriptional activator. J Biol Chem. 2001;276:38697-702 pubmed
    ..Overexpression of Haa1 does not compensate for cells lacking a functional Ace1. The lack of metalloregulation of Haa1 despite the strong sequence similarity to the copper regulatory domain of Ace1 is discussed. ..
  14. Li L, Kaplan J. A mitochondrial-vacuolar signaling pathway in yeast that affects iron and copper metabolism. J Biol Chem. 2004;279:33653-61 pubmed
    ..These results suggest that deletion of mitochondrial proteins can alter vacuolar metal homeostasis. The data also indicate that increased expression of the AFT1-regulated gene(s) can disrupt copper homeostasis. ..
  15. Pierrel F, Bestwick M, Cobine P, Khalimonchuk O, Cricco J, Winge D. Coa1 links the Mss51 post-translational function to Cox1 cofactor insertion in cytochrome c oxidase assembly. EMBO J. 2007;26:4335-46 pubmed
    ..coa1Delta cells also display a mitochondrial copper defect suggesting that Coa1 may have a direct link to copper metallation of CcO. ..
  16. Graden J, Winge D. Copper-mediated repression of the activation domain in the yeast Mac1p transcription factor. Proc Natl Acad Sci U S A. 1997;94:5550-5 pubmed
    ..Thus, Cu-regulation of Mac1p function arises from a novel Cu-specific repression of the transactivation domain function. Models for the mechanism of Cu-repression of Mac1p function will be discussed. ..