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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.

SUBMITTER: Parge HE

PROVIDER: S-EPMC49447 | biostudies-other | 1992 Jul

REPOSITORIES: biostudies-other

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Atomic structures of wild-type and thermostable mutant recombinant human Cu,Zn superoxide dismutase.

Parge H E HE Hallewell R A RA Tainer J A JA

Proceedings of the National Academy of Sciences of the United States of America 19920701 13

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 refi ...[more]

PMID: 1463506

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