title: A model for the incorporation of metal from the copper chaperone CCS into Cu,Zn superoxide dismutase.
abstract: BACKGROUND
  Recent studies have identified the human copper chaperone CCS as the presumed factor responsible for copper incorporation into superoxide dismutase (SOD). A lack of knowledge of the chaperone's three-dimensional structure has prevented understanding of how the copper might be transferred.
  
  
  RESULTS
  The three-dimensional structure of CCS was homology modelled using the periplasmic protein from the bacterial mercury-detoxification system and the structure of one subunit of the human SOD dimeric enzyme as templates. On the basis of the three-dimensional model, a mechanism for the transfer of copper from CCS to SOD is proposed that accounts for electrostatic acceptor recognition, copper storage and copper-transfer properties.
  
  
  CONCLUSIONS
  The proposed model identifies a path for copper transfer based on the presence of different metal sites characterized by sulphur ligands. Such a model permits the development of strategies able to interfere with copper incorporation in SOD, providing a possible way to prevent or arrest degeneration in the fatal motor neuron disorder amyotrophic lateral sclerosis.
authors.affiliation: Instituto Nazionale di Fisica della Materia, e Dipartimento di Biologia, Universita' di Roma Tor Vergata, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Falconi
authors.forename: M
authors.initials: M
authors.lastname: Iovino
authors.forename: A
authors.initials: A
authors.lastname: Desideri
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry; D002352:Carrier Proteins / Q000737:chemistry; D003300:Copper / Q000737:chemistry*; D006801:Humans; D008956:Models, Chemical; D018832:Molecular Chaperones / Q000737:chemistry*; D008969:Molecular Sequence Data; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity; D013482:Superoxide Dismutase / Q000737:chemistry*
chemical_list: D001426:Bacterial Proteins; C114678:CCS protein, human; D002352:Carrier Proteins; C086060:MerP protein, Bacteria; D018832:Molecular Chaperones; D011506:Proteins; D003300:Copper; D013482:Superoxide Dismutase