Atomic structures of wild-type and thermostable mutant recombinant human Cu,Zn superoxide dismutase.
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.
Parge
H E
HE
Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037.
Hallewell
R A
RA
Tainer
J A
JA
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
D011994:Recombinant Proteins; D014364:Tryptophan; D013482:Superoxide Dismutase