title: Atomic structures of wild-type and thermostable mutant recombinant human Cu,Zn superoxide dismutase.
abstract: Superoxide dismutase enzymes protect aerobic organisms from oxygen-mediated free-radical damage. Crystallographic structures of recombinant human Cu,Zn superoxide dismutase have been determined, refined, and analyzed at 2.5 A resolution for wild-type and a designed thermostable double-mutant enzyme (Cys-6----Ala, Cys-111----Ser). The 10 subunits (five dimers) in the crystallographic asymmetric unit form an unusual stable open lattice with 80-A-diameter channels. The 10 independently fit and refined subunits provide high accuracy, error analysis, and insights on loop conformations. There is a helix dipole interaction with the Zn site, and 14 residues form two or more structurally conserved side-chain to main-chain hydrogen bonds that appear critical to active-site architecture, loop conformation, and the increased stability resulting from the Cys-111----Ser mutation.
authors.affiliation: Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037.
authors.forename: H E
authors.initials: HE
authors.lastname: Parge
authors.forename: R A
authors.initials: RA
authors.lastname: Hallewell
authors.forename: J A
authors.initials: JA
authors.lastname: Tainer
mesh_terms: D003461:Crystallography; D006358:Hot Temperature; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D011994:Recombinant Proteins; D013329:Structure-Activity Relationship; D013482:Superoxide Dismutase / Q000235:genetics / Q000648:ultrastructure*; D014364:Tryptophan / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D011994:Recombinant Proteins; D014364:Tryptophan; D013482:Superoxide Dismutase