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PDBsum entry 1pm9

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protein metals Protein-protein interface(s) links
Oxidoreductase PDB id
1pm9
Jmol
Contents
Protein chains
196 a.a. *
Metals
MN3 ×2
Waters ×209
* Residue conservation analysis
PDB id:
1pm9
Name: Oxidoreductase
Title: Crystal structure of human mnsod h30n, y166f mutant
Structure: Superoxide dismutase [mn], mitochondrial. Chain: a, b. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: sod2. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PDB file)
Resolution:
1.70Å     R-factor:   0.215     R-free:   0.239
Authors: L.Fan,J.A.Tainer
Key ref:
A.S.Hearn et al. (2004). Amino acid substitution at the dimeric interface of human manganese superoxide dismutase. J Biol Chem, 279, 5861-5866. PubMed id: 14638684 DOI: 10.1074/jbc.M311310200
Date:
10-Jun-03     Release date:   16-Dec-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P04179  (SODM_HUMAN) -  Superoxide dismutase [Mn], mitochondrial
Seq:
Struc:
222 a.a.
196 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.1.15.1.1  - 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
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     oxidation-reduction process   2 terms 
  Biochemical function     superoxide dismutase activity     2 terms  

 

 
    Added reference    
 
 
DOI no: 10.1074/jbc.M311310200 J Biol Chem 279:5861-5866 (2004)
PubMed id: 14638684  
 
 
Amino acid substitution at the dimeric interface of human manganese superoxide dismutase.
A.S.Hearn, L.Fan, J.R.Lepock, J.P.Luba, W.B.Greenleaf, D.E.Cabelli, J.A.Tainer, H.S.Nick, D.N.Silverman.
 
  ABSTRACT  
 
The side chains of His30 and Tyr166 from adjacent subunits in the homotetramer human manganese superoxide dismutase (Mn-SOD) form a hydrogen bond across the dimer interface and participate in a hydrogen-bonded network that extends to the active site. 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. The observation of no additional effect upon the second mutation is an example of cooperatively interacting residues. A similar effect was observed in the thermal stability of these enzymes; the double mutant did not reduce the major unfolding transition to an extent greater than either single mutant. The crystal structures of these site-specific mutants each have unique conformational changes, but each has lost the hydrogen bond across the dimer interface, which results in a decrease in catalysis. These same mutations caused an enhancement of the dissociation of the product-inhibited complex. That is, His30 and Tyr166 in wild-type Mn-SOD act to prolong the lifetime of the inhibited complex. This would have a selective advantage in blocking a cellular overproduction of toxic H2O2.
 
  Selected figure(s)  
 
Figure 2.
FIG. 2. The least squares superimposed structures of wild-type human Mn-SOD (purple) and Y166F Mn-SOD (green) showing residues in the active site. In the mutant, the side chain of Asn171(B) emanating from the adjacent residue has rotated 130° around the C- -C- bond to form a hydrogen bond with His30. The side chain of His30 has also rotated 98° around the C- -C- bond overlapping the site of a water molecule in the wild type.
Figure 3.
FIG. 3. The least squares superimposed structures of wild-type human Mn-SOD (purple) and H30N/Y166F Mn-SOD (yellow) showing residues in the active site. Similar to Asn171(B) in the single mutant, this side chain turned toward subunit A in the double mutant, but there is no hydrogen bond between Asn171(B) and Asn30(A). Instead, the N -2 of Asn30 formed a weak hydrogen bond with the phenolic OH of Tyr34.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 5861-5866) copyright 2004.  
  Figures were selected by an automated process.  

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
19788422 M.Grey, S.Yainoy, V.Prachayasittikul, and L.Bülow (2009).
A superoxide dismutase-human hemoglobin fusion protein showing enhanced antioxidative properties.
  FEBS J, 276, 6195-6203.  
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.  
17020617 I.W.Boucher, A.M.Brzozowski, J.A.Brannigan, C.Schnick, D.J.Smith, S.A.Kyes, and A.J.Wilkinson (2006).
The crystal structure of superoxide dismutase from Plasmodium falciparum.
  BMC Struct Biol, 6, 20.
PDB code: 2bpi
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