PDBsum entry 1cb4

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protein metals Protein-protein interface(s) links
Oxidoreductase PDB id
Protein chains
151 a.a. *
_CU ×3
Waters ×138
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Crystal structure of copper, zinc superoxide dismutase
Structure: Protein (superoxide dismutase). Chain: a, b. Ec:
Source: Bos taurus. Cattle. Organism_taxid: 9913. Other_details: bovine erythrocytes
Biol. unit: Dimer (from PDB file)
2.30Å     R-factor:   0.186     R-free:   0.228
Authors: M.A.Hough,S.S.Hasnain
Key ref:
M.A.Hough and S.S.Hasnain (1999). Crystallographic structures of bovine copper-zinc superoxide dismutase reveal asymmetry in two subunits: functionally important three and five coordinate copper sites captured in the same crystal. J Mol Biol, 287, 579-592. PubMed id: 10092461 DOI: 10.1006/jmbi.1999.2610
26-Feb-99     Release date:   03-Mar-99    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P00442  (SODC_BOVIN) -  Superoxide dismutase [Cu-Zn]
152 a.a.
151 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 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
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     protein complex   11 terms 
  Biological process     reactive oxygen species metabolic process   45 terms 
  Biochemical function     antioxidant activity     10 terms  


    Added reference    
DOI no: 10.1006/jmbi.1999.2610 J Mol Biol 287:579-592 (1999)
PubMed id: 10092461  
Crystallographic structures of bovine copper-zinc superoxide dismutase reveal asymmetry in two subunits: functionally important three and five coordinate copper sites captured in the same crystal.
M.A.Hough, S.S.Hasnain.
A key feature of the generally accepted catalytic mechanism of CuZn superoxide dismutase (CuZnSOD) is the breakage of the imidazolate bridge between copper and zinc and the loss of a coordinated water molecule from copper on reduction from Cu(II) to Cu(I). Crystal structures exist for the enzyme from a number of sources in the oxidised, five coordinate copper form. For the reduced form two structures from different sources have been determined only recently but provide contradictory results. We present crystal structures of bovine CuZnSOD (BSOD) in two different space groups. The structure of the P212121 form (pBSOD), at 1.65 A resolution clearly shows one subunit with Cu in the five coordinate, oxidised form, and the other with Cu in the three coordinate form expected for the reduced state. This mixed state of pBSOD is confirmed by XANES data of these crystals. The pBSOD structure has thus captured each subunit in one of the two oxidation state conformations and thus provides direct crystallographic evidence for the superoxide dismutase mechanism involving the breakage of the imidazole bridge between Cu and Zn. A shift in the position of copper in subunit A poises the catalytic centre to undergo the first stage of catalysis via dissociation of Cu from His61 with a concomittant movement of the coordinated water molecule towards His61, which rotates by approximately 20 degrees, enabling it to form a hydrogen bond to the water molecule. The Cu-Zn separation in the reduced site is increased by approximately 0.5 A. In contrast the 2.3 A resolution structure in space group C2221 (cBSOD) shows both of the Cu atoms to be in the five coordinate, oxidised form but in this space group the whole of subunit A is significantly more disordered than subunit B. An examination of published structures of "oxidised" SODs, shows a trend towards longer Cu-Zn and Cu-His61 separations in subunit A, which together with the structures reported here indicate a potential functional asymmetry between the subunits of CuZnSODs. We also suggest that the increased separation between Cu and Zn is a precursor to breakage of His61.
  Selected figure(s)  
Figure 4.
Figure 4. Stereo 2Fo - Fc electron density map for the active site of CuZnBSOD in space group P212121. (a) Subunit A and (b) subunit B at 1.65 Å resolution, contoured at 1.5s. Copper is represented by the yellow spheres, zinc by the blue spheres. Water molecules are represented by the smaller, cyan, spheres. The shifts of water and the bridging His61 are clearly visible in (a), the reduced site.
Figure 5.
Figure 5. Superposition of the active site structures of pBSOD subunit A (red) and subunit B (blue) with cBSOD subunit A (orange) and subunit B (green). The movements of water, His61 and Cu are clearly visible in subunit A (red) of pBSOD.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1999, 287, 579-592) copyright 1999.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference Google scholar

  PubMed id Reference
20516618 I.Ascone, C.Savino, R.Kahn, and R.Fourme (2010).
Flexibility of the Cu,Zn superoxide dismutase structure investigated at 0.57 GPa.
  Acta Crystallogr D Biol Crystallogr, 66, 654-663.
PDB code: 3hw7
20029110 L.Giachini, G.Veronesi, F.Francia, G.Venturoli, and F.Boscherini (2010).
Synergic approach to XAFS analysis for the identification of most probable binding motifs for mononuclear zinc sites in metalloproteins.
  J Synchrotron Radiat, 17, 41-52.  
  19886398 A.Valdivia, S.Pérez-Alvarez, J.D.Aroca-Aguilar, I.Ikuta, and J.Jordán (2009).
Superoxide dismutases: a physiopharmacological update.
  J Physiol Biochem, 65, 195-208.  
18425534 H.J.Kim, N.Kato, S.Kim, and B.Triplett (2008).
Cu/Zn superoxide dismutases in developing cotton fibers: evidence for an extracellular form.
  Planta, 228, 281-292.  
18521547 J.Liu, L.Ma, S.Yin, and F.Hong (2008).
Effects of Ce3+ on conformation and activity of superoxide dismutase.
  Biol Trace Elem Res, 125, 170-178.  
18645238 M.Yogavel, P.C.Mishra, J.Gill, P.K.Bhardwaj, S.Dutt, S.Kumar, P.S.Ahuja, and A.Sharma (2008).
Structure of a superoxide dismutase and implications for copper-ion chelation.
  Acta Crystallogr D Biol Crystallogr, 64, 892-901.  
17305404 B.W.Meier, J.D.Gomez, O.V.Kirichenko, and J.A.Thompson (2007).
Mechanistic basis for inflammation and tumor promotion in lungs of 2,6-di-tert-butyl-4-methylphenol-treated mice: electrophilic metabolites alkylate and inactivate antioxidant enzymes.
  Chem Res Toxicol, 20, 199-207.  
17919319 R.R.Gabdoulline, M.Stein, and R.C.Wade (2007).
qPIPSA: relating enzymatic kinetic parameters and interaction fields.
  BMC Bioinformatics, 8, 373.  
16688583 A.Chiumiento, A.Dominguez, S.Lamponi, R.Villalonga, and R.Barbucci (2006).
Anti-inflammatory properties of superoxide dismutase modified with carboxymetil-cellulose polymer and hydrogel.
  J Mater Sci Mater Med, 17, 427-435.  
16952188 M.Isobe, H.Kai, T.Kurahashi, S.Suwan, S.Pitchayawasin-Thapphasaraphong, T.Franz, N.Tani, K.Higashi, and H.Nishida (2006).
The molecular mechanism of the termination of insect diapause, part 1: A timer protein, TIME-EA4, in the diapause eggs of the silkworm Bombyx mori is a metallo-glycoprotein.
  Chembiochem, 7, 1590-1598.  
16233812 H.Nagami, N.Yoshimoto, H.Umakoshi, T.Shimanouchi, and R.Kuboi (2005).
Liposome-assisted activity of superoxide dismutase under oxidative stress.
  J Biosci Bioeng, 99, 423-428.  
15952898 J.S.Valentine, P.A.Doucette, and S.Zittin Potter (2005).
Copper-zinc superoxide dismutase and amyotrophic lateral sclerosis.
  Annu Rev Biochem, 74, 563-593.  
15328354 F.Dupeyrat, C.Vidaud, A.Lorphelin, and C.Berthomieu (2004).
Long distance charge redistribution upon Cu,Zn-superoxide dismutase reduction: significance for dismutase function.
  J Biol Chem, 279, 48091-48101.  
15333927 R.M.Cardoso, C.H.Silva, A.P.Ulian de Araújo, T.Tanaka, M.Tanaka, and R.C.Garratt (2004).
Structure of the cytosolic Cu,Zn superoxide dismutase from Schistosoma mansoni.
  Acta Crystallogr D Biol Crystallogr, 60, 1569-1578.
PDB codes: 1to4 1to5
12485776 B.Ge, F.W.Scheller, and F.Lisdat (2003).
Electrochemistry of immobilized CuZnSOD and FeSOD and their interaction with superoxide radicals.
  Biosens Bioelectron, 18, 295-302.  
12637583 L.Royle, A.Roos, D.J.Harvey, M.R.Wormald, D.van Gijlswijk-Janssen, e.l.-.R.M.Redwan, I.A.Wilson, M.R.Daha, R.A.Dwek, and P.M.Rudd (2003).
Secretory IgA N- and O-glycans provide a link between the innate and adaptive immune systems.
  J Biol Chem, 278, 20140-20153.  
12906825 M.A.Hough, and S.S.Hasnain (2003).
Structure of fully reduced bovine copper zinc superoxide dismutase at 1.15 A.
  Structure, 11, 937-946.
PDB code: 1q0e
11952792 L.Banci, I.Bertini, F.Cramaro, R.Del Conte, and M.S.Viezzoli (2002).
The solution structure of reduced dimeric copper zinc superoxide dismutase. The structural effects of dimerization.
  Eur J Biochem, 269, 1905-1915.
PDB code: 1l3n
11468394 M.J.Ellis, F.E.Dodd, R.W.Strange, M.Prudêncio, G.Sawers, R.R.Eady, and S.S.Hasnain (2001).
X-ray structure of a blue copper nitrite reductase at high pH and in copper-free form at 1.9 A resolution.
  Acta Crystallogr D Biol Crystallogr, 57, 1110-1118.
PDB codes: 1hau 1haw
11567153 Q.Hao (2001).
Phasing from an envelope.
  Acta Crystallogr D Biol Crystallogr, 57, 1410-1414.  
11679732 W.Liu, P.W.Li, G.P.Li, R.H.Zhu, and D.C.Wang (2001).
Overexpression, purification, crystallization and preliminary X-ray diffraction analysis of Cu,Zn superoxide dismutase from Peking duck.
  Acta Crystallogr D Biol Crystallogr, 57, 1646-1649.  
10944337 D.M.Ockwell, M.A.Hough, J.G.Grossmann, S.S.Hasnain, and Q.Hao (2000).
Implementation of cluster analysis for ab initio phasing using the molecular envelope from solution X-ray scattering.
  Acta Crystallogr D Biol Crystallogr, 56, 1002-1006.  
11076515 E.Aronoff-Spencer, C.S.Burns, N.I.Avdievich, G.J.Gerfen, J.Peisach, W.E.Antholine, H.L.Ball, F.E.Cohen, S.B.Prusiner, and G.L.Millhauser (2000).
Identification of the Cu2+ binding sites in the N-terminal domain of the prion protein by EPR and CD spectroscopy.
  Biochemistry, 39, 13760-13771.  
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. Where a reference describes a PDB structure, the PDB code is shown on the right.