PDBsum entry 1rfw

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Oxidoreductase PDB id
Protein chains
198 a.a.
MW1 ×2
Waters ×154
Superseded by: 1szx 1szx
PDB id:
Name: Oxidoreductase
Title: Role of hydrogen bonding in the active site of human manganese superoxide dismutase
Structure: Superoxide dismutase [mn]. Chain: a, b. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Gene: sod2. Expressed in: escherichia coli.
Biol. unit: Tetramer (from PDB file)
2.20Å     R-factor:   0.249     R-free:   0.268
Authors: W.B.Greenleaf,M.E.Stroupe,D.E.Cabelli,J.R.Lepock,J.A.Tainer, H.S.Nick,D.S.Silverman
Key ref:
W.B.Greenleaf et al. (2004). Role of hydrogen bonding in the active site of human manganese superoxide dismutase. Biochemistry, 43, 7038-7045. PubMed id: 15170341 DOI: 10.1021/bi049888k
10-Nov-03     Release date:   25-Nov-03    
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Protein chains
Pfam   ArchSchema ?
P04179  (SODM_HUMAN) -  Superoxide dismutase [Mn], mitochondrial
222 a.a.
198 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.  - Superoxide dismutase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 2 superoxide + 2 H+ = O2 + H2O2
2 × superoxide
+ 2 × H(+)
= O(2)
+ H(2)O(2)
      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    
DOI no: 10.1021/bi049888k Biochemistry 43:7038-7045 (2004)
PubMed id: 15170341  
Role of hydrogen bonding in the active site of human manganese superoxide dismutase.
W.B.Greenleaf, J.J.Perry, A.S.Hearn, D.E.Cabelli, J.R.Lepock, M.E.Stroupe, J.A.Tainer, H.S.Nick, D.N.Silverman.
The side chain of Gln143, a conserved residue in manganese superoxide dismutase (MnSOD), forms a hydrogen bond with the manganese-bound solvent and is critical in maintaining catalytic activity. The side chains of Tyr34 and Trp123 form hydrogen bonds with the carboxamide of Gln143. We have replaced Tyr34 and Trp123 with Phe in single and double mutants of human MnSOD and measured their catalytic activity by stopped-flow spectrophotometry and pulse radiolysis. The replacements of these side chains inhibited steps in the catalysis as much as 50-fold; in addition, they altered the gating between catalysis and formation of a peroxide complex to yield a more product-inhibited enzyme. The replacement of both Tyr34 and Trp123 in a double mutant showed that these two residues interact cooperatively in maintaining catalytic activity. The crystal structure of Y34F/W123F human MnSOD at 1.95 A resolution suggests that this effect is not related to a conformational change in the side chain of Gln143, which does not change orientation in Y34F/W123F, but rather to more subtle electronic effects due to the loss of hydrogen bonding to the carboxamide side chain of Gln143. Wild-type MnSOD containing Trp123 and Tyr34 has approximately the same thermal stability compared with mutants containing Phe at these positions, suggesting the hydrogen bonds formed by these residues have functional rather than structural roles.

Literature references that cite this PDB file's key reference

  PubMed id Reference
19265433 J.J.Perry, A.S.Hearn, D.E.Cabelli, H.S.Nick, J.A.Tainer, and D.N.Silverman (2009).
Contribution of human manganese superoxide dismutase tyrosine 34 to structure and catalysis.
  Biochemistry, 48, 3417-3424.
PDB codes: 1zsp 1zte 1zuq 2p4k
17912757 R.Wintjens, D.Gilis, and M.Rooman (2008).
Mn/Fe superoxide dismutase interaction fingerprints and prediction of oligomerization and metal cofactor from sequence.
  Proteins, 70, 1564-1577.  
17174478 J.J.Perry, L.Fan, and J.A.Tainer (2007).
Developing master keys to brain pathology, cancer and aging from the structural biology of proteins controlling reactive oxygen species and DNA repair.
  Neuroscience, 145, 1280-1299.  
16999822 K.Chockalingam, J.Luba, H.S.Nick, D.N.Silverman, and H.Zhao (2006).
Engineering and characterization of human manganese superoxide dismutase mutants with high activity and low product inhibition.
  FEBS J, 273, 4853-4861.  
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