PDBsum entry 2qkc

Oxidoreductase

PDB id: 2qkc

Contents

Protein chains

196 a.a. *

Metals

_MN ×2

Waters ×116

* Residue conservation analysis

PDB id:

2qkc

Name:

Oxidoreductase

Title:

Structural and kinetic study of the differences between human and e.Coli manganese superoxide dismutases

Structure:

Superoxide dismutase [mn]. Chain: a, c. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: sod2. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.30Å R-factor: 0.199 R-free: 0.206

Authors:

J.Zheng,J.F.Domsic,D.Cabelli,R.Mckenna,D.N.Silverman

Key ref:

J.Zheng et al. (2007). Structural and kinetic study of differences between human and Escherichia coli manganese superoxide dismutases. Biochemistry, 46, 14830-14837. PubMed id: 18044968

Date:

10-Jul-07 Release date: 29-Jul-08

Protein chains

P04179  (SODM_HUMAN) -  Superoxide dismutase [Mn], mitochondrial from Homo sapiens

Seq: 222 a.a.

Struc: 196 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.1.15.1.1 - superoxide dismutase.
• Reaction: 2 superoxide + 2 H⁺ = H2O2 + O2
• Cofactor: Fe cation or Mn(2+) or (Zn(2+) and Cu cation)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

Biochemistry 46:14830-14837 (2007)

PubMed id: 18044968

Structural and kinetic study of differences between human and Escherichia coli manganese superoxide dismutases.

J.Zheng, J.F.Domsic, D.Cabelli, R.McKenna, D.N.Silverman.

ABSTRACT

Human manganese superoxide dismutase (MnSOD) is characterized by a product inhibition stronger than that observed in bacterial forms of MnSOD. Previous studies show that the conserved, active-site residue Tyr34 mediates product inhibition; however, the protein environment of Tyr34 is different in human and Escherichia coli MnSOD. We have prepared two site-specific mutants of human MnSOD with replacements of Phe66 with Ala and Leu (F66A and F66L, respectively), altering the surroundings of Tyr34. Pulse radiolysis was used to generate superoxide, and measurements of catalysis were taken in single-turnover experiments by observing the visible absorbance of species of MnSOD and under catalytic conditions observing the absorbance of superoxide. The mutation of Phe66 to Leu resulted in a mutant of human MnSOD with weakened product inhibition resembling that of E. coli MnSOD. Moreover, the mechanism of this weakened product inhibition was similar to that in E. coli MnSOD, specifically a decrease in the rate constant for the oxidative addition of superoxide to Mn2+MnSOD leading to the formation of the peroxide-inhibited enzyme. In addition, the crystal structures of both mutants have been determined and compared to those of wild-type human and E. coli MnSOD. The crystallographic data suggest that the solvent structure and its mobility as well as side chain conformations may affect the extent of product inhibition. These data emphasize the role of residue 66 in catalysis and inhibition and provide a structural explanation for differences in catalytic properties between human and certain bacterial forms of MnSOD.