PDBsum entry 2af2

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protein metals Protein-protein interface(s) links
Oxidoreductase PDB id
Protein chain
153 a.a. *
_ZN ×2
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Solution structure of disulfide reduced and copper depleted human superoxide dismutase
Structure: Superoxide dismutase [cu-zn]. Chain: a, b. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: sod1. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 30 models
Authors: L.Banci,I.Bertini,F.Cantini,N.D'Amelio,E.Gaggelli, Structural Proteomics In Europe (Spine)
Key ref:
L.Banci et al. (2006). Human SOD1 before harboring the catalytic metal: solution structure of copper-depleted, disulfide-reduced form. J Biol Chem, 281, 2333-2337. PubMed id: 16291742 DOI: 10.1074/jbc.M506497200
25-Jul-05     Release date:   15-Nov-05    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P00441  (SODC_HUMAN) -  Superoxide dismutase [Cu-Zn]
154 a.a.
153 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
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   20 terms 
  Biological process     cellular response to potassium ion   66 terms 
  Biochemical function     antioxidant activity     13 terms  


    Added reference    
DOI no: 10.1074/jbc.M506497200 J Biol Chem 281:2333-2337 (2006)
PubMed id: 16291742  
Human SOD1 before harboring the catalytic metal: solution structure of copper-depleted, disulfide-reduced form.
L.Banci, I.Bertini, F.Cantini, N.D'Amelio, E.Gaggelli.
SOD1 has to undergo several post-translational modifications before reaching its mature form. The protein requires insertion of zinc and copper atoms, followed by the formation of a conserved S-S bond between Cys-57 and Cys-146 (human numbering), which makes the protein fully active. In this report an NMR structural investigation of the reduced SH-SH form of thermostable E,Zn-as-SOD1 (E is empty; as is C6A, C111S) is reported, characterizing the protein just before the last step leading to the mature form. The structure is compared with that of the oxidized S-S form as well as with that of the yeast SOD1 complexed with its copper chaperone, CCS. Local conformational rearrangements upon disulfide bridge reduction are localized in the region near Cys-57 that is completely exposed to the solvent in the present structure, at variance with the oxidized forms. There is a local disorder around Cys-57 that may serve for protein-protein recognition and may possibly be involved in intermolecular S-S bonds in familial amyotrophic lateral sclerosis-related SOD1 mutants. The structure allows us to further discuss the copper loading mechanism in SOD1.
  Selected figure(s)  
Figure 1.
Solution structure of E,Zn-hasSOD1^SH-SH. The side chains of Cys-57 and Cys-146 are shown as sticks.
Figure 3.
Structure superimposition of E,Zn-hasSOD1^SH-SH (light gray) and yeast SOD1 interacting with yeast CCS (black). Some key residues are highlighted (gray for E,Zn-hasSOD1^SH-SH and black for yeast SOD1): the carbonyl of Ala-230 involved in an H-bond with Arg-143 in the yeast complex, Cys-229 and Cys-231 belonging to CCS, Cys-57 and Cys-146 belonging to SOD1 structures.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 2333-2337) copyright 2006.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19669620 D.H.Jones, S.E.Cellitti, X.Hao, Q.Zhang, M.Jahnz, D.Summerer, P.G.Schultz, T.Uno, and B.H.Geierstanger (2010).
Site-specific labeling of proteins with NMR-active unnatural amino acids.
  J Biomol NMR, 46, 89.  
19800308 A.Galaleldeen, R.W.Strange, L.J.Whitson, S.V.Antonyuk, N.Narayana, A.B.Taylor, J.P.Schuermann, S.P.Holloway, S.S.Hasnain, and P.J.Hart (2009).
Structural and biophysical properties of metal-free pathogenic SOD1 mutants A4V and G93A.
  Arch Biochem Biophys, 492, 40-47.
PDB codes: 2wko 3gzo 3gzp 3gzq
19651777 A.Tiwari, A.Liba, S.H.Sohn, S.V.Seetharaman, O.Bilsel, C.R.Matthews, P.J.Hart, J.S.Valentine, and L.J.Hayward (2009).
Metal deficiency increases aberrant hydrophobicity of mutant superoxide dismutases that cause amyotrophic lateral sclerosis.
  J Biol Chem, 284, 27746-27758.  
19023603 D.C.Soares, P.N.Barlow, D.J.Porteous, and R.S.Devon (2009).
An interrupted beta-propeller and protein disorder: structural bioinformatics insights into the N-terminus of alsin.
  J Mol Model, 15, 113-122.  
19542232 J.M.Leitch, L.T.Jensen, S.D.Bouldin, C.E.Outten, P.J.Hart, and V.C.Culotta (2009).
Activation of Cu,Zn-superoxide dismutase in the absence of oxygen and the copper chaperone CCS.
  J Biol Chem, 284, 21863-21871.  
19271992 M.Chattopadhyay, and J.S.Valentine (2009).
Aggregation of copper-zinc superoxide dismutase in familial and sporadic ALS.
  Antioxid Redox Signal, 11, 1603-1614.  
19596823 S.V.Seetharaman, M.Prudencio, C.Karch, S.P.Holloway, D.R.Borchelt, and P.J.Hart (2009).
Immature copper-zinc superoxide dismutase and familial amyotrophic lateral sclerosis.
  Exp Biol Med (Maywood), 234, 1140-1154.  
19007184 A.N.Barry, K.M.Clark, A.Otoikhian, W.A.van der Donk, and N.J.Blackburn (2008).
Selenocysteine positional variants reveal contributions to copper binding from cysteine residues in domains 2 and 3 of human copper chaperone for superoxide dismutase.
  Biochemistry, 47, 13074-13083.  
19436494 A.Nordlund, and M.Oliveberg (2008).
SOD1-associated ALS: a promising system for elucidating the origin of protein-misfolding disease.
  HFSP J, 2, 354-364.  
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.  
17888947 B.R.Roberts, J.A.Tainer, E.D.Getzoff, D.A.Malencik, S.R.Anderson, V.C.Bomben, K.R.Meyers, P.A.Karplus, and J.S.Beckman (2007).
Structural characterization of zinc-deficient human superoxide dismutase and implications for ALS.
  J Mol Biol, 373, 877-890.
PDB code: 2r27
17255946 C.K.Bruns, and R.R.Kopito (2007).
Impaired post-translational folding of familial ALS-linked Cu, Zn superoxide dismutase mutants.
  EMBO J, 26, 855-866.  
16880213 M.C.Carroll, C.E.Outten, J.B.Proescher, L.Rosenfeld, W.H.Watson, L.J.Whitson, P.J.Hart, L.T.Jensen, and V.Cizewski Culotta (2006).
The effects of glutaredoxin and copper activation pathways on the disulfide and stability of Cu,Zn superoxide dismutase.
  J Biol Chem, 281, 28648-28656.  
16516535 P.J.Hart (2006).
Pathogenic superoxide dismutase structure, folding, aggregation and turnover.
  Curr Opin Chem Biol, 10, 131-138.  
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 codes are shown on the right.