The structure of human mitochondrial manganese superoxide dismutase reveals a novel tetrameric interface of two 4-helix bundles

  title={The structure of human mitochondrial manganese superoxide dismutase reveals a novel tetrameric interface of two 4-helix bundles},
  author={Gloria E. O. Borgstahl and Hans E. Parge and Michael J. Hickey and Wayne F. Beyer and R. A. Hallewell and John A. Tainer},

Amino Acid Substitution at the Dimeric Interface of Human Manganese Superoxide Dismutase*

Compared with wild-type Mn-SOD, the site-specific mutants H30N, Y166F, and the corresponding double mutant showed 10-fold decreases in steady-state constants for catalysis measured by pulse radiolysis.

Subunit interaction in extracellular superoxide dismutase: Effects of mutations in the N‐terminal domain

The N‐terminal domain of EC‐SOD has already been studied using the fusion protein FusNN, which forms a well‐defined three‐dimensional structure, which probably contains α‐helical elements and is responsible for the tetramerization of the protein.

Contribution of human manganese superoxide dismutase tyrosine 34 to structure and catalysis.

Structural and catalytic roles of the highly conserved active-site residue Tyr34 are examined, based upon structure-function studies of MnSOD enzymes with mutations at this site, and an intermediate in catalysis is observed, which has not been reported previously.

Engineering of an intersubunit disulfide bridge in the iron-superoxide dismutase of Mycobacterium tuberculosis.

The mutant protein was found to be less stable than the wild type as judged by susceptibility to denaturation in the presence of guanidine hydrochloride and decreased stability probably results from formation of a disulfide bridge with a suboptimal torsion angle and exclusion of solvent molecules from the dimer interface.

Nickel superoxide dismutase structure and mechanism.

The 1.30 A resolution crystal structure of nickel superoxide dismutase (NiSOD) identifies a novel SOD fold, assembly, and Ni active site that provides almost all interactions critical for metal binding and catalysis, and thus will likely be diagnostic of NiSODs.

Role of a glutamate bridge spanning the dimeric interface of human manganese superoxide dismutase.

Results suggest that Glu162 at the tetrameric interface in human MnSOD supports stability and efficient catalysis and has a significant role in regulating product inhibition.

A Glutamate Bridge Is Essential for Dimer Stability and Metal Selectivity in Manganese Superoxide Dismutase*

In Escherichia coli manganese superoxide dismutase (MnSOD), the absolutely conserved Glu170 of one monomer is hydrogen-bonded to the Mn ligand His171 of the other monomer, forming a double bridge at the dimer interface, and the mutant protein occurs as a mixture of dimer and monomer species.

Structures of native and Fe-substituted SOD2 from Saccharomyces cerevisiae.

The surface-potential distribution of SOD2 revealed a conserved positively charged electrostatic zone in the proximity of the active site that probably functions in the same way as in Cu/Zn-SODs by facilitating the diffusion of the superoxide anion to the metal ion.



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

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).

Manganese and iron superoxide dismutases are structural homologs.

The crystal structure of a tetrameric manganese superoxide dismutase from a thermophilic bacterium, Thermus thermophilus HB8, has been determined at 4.4-A resolution by local averaging of electron

The 2.1-A resolution structure of iron superoxide dismutase from Pseudomonas ovalis.

The 2.1-A resolution crystal structure of native uncomplexed iron superoxide dismutase (EC from Pseudomonas ovalis was solved and refined to a final R factor of 24%. The dimeric structure

The structure of iron superoxide dismutase from Pseudomonas ovalis complexed with the inhibitor azide.

Comparisons with MnSOD show that a different glutamine which possesses the same interactions in the active site as Gln70 in FeSOD is conserved at position 154 in the overall SOD sequence, implying that while manganese and FeS ODs are structural homologues in a global sense, their functional and evolutionary relationship is that of second-site mutation revertants.

Changes in crystallographic structure and thermostability of a Cu,Zn superoxide dismutase mutant resulting from the removal of a buried cysteine.

The results differentiate between the effects of reversible and irreversible processes as they impact the design of thermostable proteins and suggest that relatively subtle concerted shifts can significantly reduce the energetic cost of evolutionary variation in internal residues of proteins with Greek key beta-barrel folds.

Faster superoxide dismutase mutants designed by enhancing electrostatic guidance

It is shown that site-specific mutants that increase local positive charge while maintaining this orienting network (Glu→Gin) have faster reaction rates and increased ionic-strength dependence, matching brownian dynamics simulations incorporating electrostatic terms.