title: Dominant role of copper in the kinetic stability of Cu/Zn superoxide dismutase.
abstract: Mutations in Cu/Zn superoxide dismutase (SOD) are involved in some cases of familial amyotrophic lateral sclerosis, and it appears that misfolding and aggregation, perhaps mediated by abnormal binding or loss of copper (Cu) and/or zinc (Zn), may play a pathological role. It is known that the absence of both metals kinetically destabilizes wild type and mutant SOD leading to a 60-fold increase in their rate of unfolding. Here, the individual contributions of Cu and Zn to the kinetic stability of SOD were investigated, and the results show that Cu plays a greater role. Thus, the deficiency of Cu or Zn, especially the former, will compromise the kinetic stability of SOD, thereby increasing the probability that pathogenic mutants and even the WT protein may misfold and self-assemble into toxic species.
authors.affiliation: Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, 110 8th Street, Troy, NY 12180, USA.
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Lynch
authors.forename: Wilfredo
authors.initials: W
authors.lastname: Colón
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology; D001665:Binding Sites; D003300:Copper / Q000502:physiology*; D004795:Enzyme Stability / Q000502:physiology; D006801:Humans; D007700:Kinetics; D011489:Protein Denaturation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D013482:Superoxide Dismutase / Q000737:chemistry / Q000378:metabolism*; D013816:Thermodynamics; D015032:Zinc / Q000737:chemistry* / Q000502:physiology*
chemical_list: D003300:Copper; D013482:Superoxide Dismutase; D015032:Zinc