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PDBsum entry 4sod

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Oxidoreductase(superoxide acceptor) PDB id
4sod
Jmol
Contents
Protein chain
172 a.a.
Theoretical model
PDB id:
4sod
Name: Oxidoreductase(superoxide acceptor)
Structure: Cu,zn superoxide dismutase mutant with cys 6 replaced by ala and cys 111 replaced by ser (c6a,c111s) with an 18-residue heparin-binding peptide fused to thE C-terminus (theoretical model)
Source: Human (homo sapiens) recombinant protein (cu,zn form) expressed in escherichia coli
Ensemble: 2 models
Authors: L.A.Kuhn,C.L.Fisher,J.A.Tainer
Key ref: M.Boissinot et al. (1993). Rational design and expression of a heparin-targeted human superoxide dismutase. Biochem Biophys Res Commun, 190, 250-256. PubMed id: 8422249
Date:
14-Jan-93     Release date:   30-Apr-94    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
No UniProt id for this chain
Struc: 171 a.a.
Key:    Secondary structure

 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

 

 
    Added reference    
 
 
Biochem Biophys Res Commun 190:250-256 (1993)
PubMed id: 8422249  
 
 
Rational design and expression of a heparin-targeted human superoxide dismutase.
M.Boissinot, L.A.Kuhn, P.Lee, C.L.Fisher, Y.Wang, R.A.Hallewell, J.A.Tainer.
 
  ABSTRACT  
 
In order to improve the therapeutic effectiveness of human Cu,Zn superoxide dismutase (HSOD) by targeting it to cell surfaces and increasing its circulatory half-life, we have designed and expressed a heparin-binding derivative of HSOD. This design was based on the idea that structurally independent protein units, HSOD and the heparin-binding A+ helix from protein C inhibitor, could be combined with a carefully chosen linker, GlyProGly, to form a stable, bifunctional protein. The chimeric HSOD-GlyProGly-A+ protein was expressed and secreted to the periplasm of E. coli and had normal SOD activity. HSOD-GlyProGly-A+ had a significantly increased retention time relative to wild-type HSOD on a heparin affinity column, indicating that it was successfully targeted to heparin, and this binding was maintained at physiological ionic strength. When administered to mice, HSOD-GlyProGly-A+ had a half-life of approximately 15 minutes, twice that of wild-type HSOD. Our rational design approach should be generally applicable to the creation of bifunctional chimeric molecules.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
16790290 D.V.Ratnam, D.D.Ankola, V.Bhardwaj, D.K.Sahana, and M.N.Kumar (2006).
Role of antioxidants in prophylaxis and therapy: A pharmaceutical perspective.
  J Control Release, 113, 189-207.  
12657855 K.Takakura, W.Xiaohong, K.Takeuchi, Y.Yasuda, and S.Fukuda (2003).
Deactivation of norepinephrine by peroxynitrite as a new pathogenesis in the hypotension of septic shock.
  Anesthesiology, 98, 928-934.  
11940765 K.Takakura, T.Taniguchi, I.Muramatsu, K.Takeuchi, and S.Fukuda (2002).
Modification of alpha1 -adrenoceptors by peroxynitrite as a possible mechanism of systemic hypotension in sepsis.
  Crit Care Med, 30, 894-899.  
11291598 V.R.Muzykantov (2001).
Delivery of antioxidant enzyme proteins to the lung.
  Antioxid Redox Signal, 3, 39-62.  
11245904 V.R.Muzykantov (2001).
Targeting of superoxide dismutase and catalase to vascular endothelium.
  J Control Release, 71, 1.  
11101304 E.Doss-Pepe, P.Deprez, N.C.Inestrosa, and B.Brodsky (2000).
Interaction of collagen-like peptide models of asymmetric acetylcholinesterase with glycosaminoglycans: spectroscopic studies of conformational changes and stability.
  Biochemistry, 39, 14884-14892.  
9988743 M.Houston, A.Estevez, P.Chumley, M.Aslan, S.Marklund, D.A.Parks, and B.A.Freeman (1999).
Binding of xanthine oxidase to vascular endothelium. Kinetic characterization and oxidative impairment of nitric oxide-dependent signaling.
  J Biol Chem, 274, 4985-4994.  
9171332 M.Boissinot, S.Karnas, J.R.Lepock, D.E.Cabelli, J.A.Tainer, E.D.Getzoff, and R.A.Hallewell (1997).
Function of the Greek key connection analysed using circular permutants of superoxide dismutase.
  EMBO J, 16, 2171-2178.  
7779581 B.Gao, S.C.Flores, and J.M.McCord (1995).
A site-directed mutant of Cu,Zn-superoxide dismutase modeled after native extracellular superoxide dismutase.
  Biol Trace Elem Res, 47, 95.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.