title: Superoxide-dependent peroxidase activity of H48Q: a superoxide dismutase variant associated with familial amyotrophic lateral sclerosis.
abstract: Approximately 20% of cases of familial amyotrophic lateral sclerosis are caused by dominant mutations in the Cu,Zn superoxide dismutase. One such mutant, in which histidine #48 has been replaced by glutamine (H48Q), exhibits a novel activity. It can react sequentially with O2- and H2O2 to generate a potent oxidant at its active site, possibly Cu(II)-OH, which then can oxidize urate to the corresponding radical. This O2- -dependent peroxidase activity exerted on a substrate peculiar to motor neurons may be the toxic gain of function which leads to the deleterious consequences of this mutation. G93A, G93R, and E100G were also examined and found not to exert this O2- -dependent peroxidase activity.
authors.affiliation: Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: S I
authors.initials: SI
authors.lastname: Liochev
authors.forename: L L
authors.initials: LL
authors.lastname: Chen
authors.forename: R A
authors.initials: RA
authors.lastname: Hallewell
authors.forename: I
authors.initials: I
authors.lastname: Fridovich
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000235:genetics; D001665:Binding Sites; D003001:Cloning, Molecular; D003300:Copper / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D004926:Escherichia coli; D006861:Hydrogen Peroxide / Q000378:metabolism; D009154:Mutation; D010084:Oxidation-Reduction; D011994:Recombinant Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism* / Q000494:pharmacology; D014527:Uric Acid / Q000494:pharmacology; D019820:Xanthine / Q000378:metabolism; D014969:Xanthine Oxidase
chemical_list: D003574:Cytochrome c Group; D011994:Recombinant Proteins; D013481:Superoxides; D019820:Xanthine; D014527:Uric Acid; D003300:Copper; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase