PDBsum entry 2c9v

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
Protein chain
153 a.a. *
SO4 ×5
_NA ×2
_CU ×2
_ZN ×2
Waters ×597
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Atomic resolution structure of cu-zn human superoxide dismutase
Structure: Superoxide dismutase [cu-zn]. Chain: a, f. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Tissue: blood. Expressed in: saccharomyces cerevisiae. Expression_system_taxid: 4932
Biol. unit: Dimer (from PDB file)
1.07Å     R-factor:   0.132     R-free:   0.158
Authors: R.W.Strange,S.V.Antonyuk,M.A.Hough,P.A.Doucette, J.S.Valentine,S.S.Hasnain
Key ref:
R.W.Strange et al. (2006). Variable Metallation of Human Superoxide Dismutase: Atomic Resolution Crystal Structures of Cu-Zn, Zn-Zn and As-isolated Wild-type Enzymes. J Mol Biol, 356, 1152-1162. PubMed id: 16406071 DOI: 10.1016/j.jmb.2005.11.081
14-Dec-05     Release date:   20-Dec-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

 Enzyme reactions 
   Enzyme class: E.C.  - Superoxide dismutase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 2 superoxide + 2 H+ = O2 + H2O2
2 × superoxide
+ 2 × H(+)
Bound ligand (Het Group name = SO4)
matches with 40.00% similarity
+ 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   16 terms 
  Biological process     reactive oxygen species metabolic process   62 terms 
  Biochemical function     antioxidant activity     12 terms  


    Added reference    
DOI no: 10.1016/j.jmb.2005.11.081 J Mol Biol 356:1152-1162 (2006)
PubMed id: 16406071  
Variable Metallation of Human Superoxide Dismutase: Atomic Resolution Crystal Structures of Cu-Zn, Zn-Zn and As-isolated Wild-type Enzymes.
R.W.Strange, S.V.Antonyuk, M.A.Hough, P.A.Doucette, J.S.Valentine, S.S.Hasnain.
Human Cu-Zn superoxide dismutase (SOD1) protects cells from the effects of oxidative stress. Mutations in SOD1 are linked to the familial form of amyotrophic lateral sclerosis. Several hypotheses for their toxicity involve the mis-metallation of the enzyme. We present atomic-resolution crystal structures and biophysical data for human SOD1 in three metallation states: Zn-Zn, Cu-Zn and as-isolated. These data represent the first atomic-resolution structures for human SOD1, the first structure of a reduced SOD1, and the first structure of a fully Zn-substituted SOD1 enzyme. Recombinantly expressed as-isolated SOD1 contains a mixture of Zn and Cu at the Cu-binding site. The Zn-Zn structure appears to be at least as stable as the correctly (Cu-Zn) metallated enzyme. These data raise the possibility that in a cellular environment with low availability of free copper, Zn-Zn may be the preferred metallation state of SOD1 prior to its interaction with the copper chaperone.
  Selected figure(s)  
Figure 4.
Figure 4. The water network at the active site of the re-constituted Cu-Zn enzyme, monomer A. A sulphate ion sits on the surface of the molecule at the substrate entry site. A dual-occupancy water molecule (W1) is 2.6 Å from Cu(II) and 3.7 Å from the position of the Cu(I) atom. W1 is linked to the Thr137 O protein backbone via a H bond and to the Gly141 O atom via H bonding to a second water molecule, W2, which is also linked (2.8 Å) to water molecule W3, the Gly141 residue and to a sulphate ion on the protein surface (2.6 Å). W3 forms a long (2.9 Å) H-bond to the Ny group of Arg143. A full-occupancy water molecule, W5, is in direct contact with the protein main chain, linked to the Lys136 O and His63 N atoms. W5 and W3 are linked by W4, which is 4.4 Å from Cu(II). The Gly141 O and Arg143 Ne atoms are bridged by W6. Finally, W7, 5.3 Å from the (Zn site) Zn atom and a highly conserved water molecule in all three structures (and in bovine SOD), has H bonds with the secondary bridge residue Asp124 Od (2.8 Å) and with Gly85 N (2.9 Å) and Gly72 O (2.8 Å) atoms.
Figure 6.
Figure 6. Thermal probability ellipsoids for the active sites of the (a) Cu-Zn, (b) as-isolated and (c) Zn-Zn structures. The sites show only limited anisotropy. The highly anisotropic ellipsoid for Cu(II) in the Cu-Zn structure is indicative of a range of positions adopted by the metal ion.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2006, 356, 1152-1162) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20404910 A.K.Svensson, O.Bilsel, C.Kayatekin, J.A.Adefusika, J.A.Zitzewitz, and C.R.Matthews (2010).
Metal-free ALS variants of dimeric human Cu,Zn-superoxide dismutase have enhanced populations of monomeric species.
  PLoS One, 5, e10064.  
20953194 D.A.Bosco, G.Morfini, N.M.Karabacak, Y.Song, F.Gros-Louis, P.Pasinelli, H.Goolsby, B.A.Fontaine, N.Lemay, D.McKenna-Yasek, M.P.Frosch, J.N.Agar, J.P.Julien, S.T.Brady, and R.H.Brown (2010).
Wild-type and mutant SOD1 share an aberrant conformation and a common pathogenic pathway in ALS.
  Nat Neurosci, 13, 1396-1403.  
21098299 J.R.Auclair, K.J.Boggio, G.A.Petsko, D.Ringe, and J.N.Agar (2010).
Strategies for stabilizing superoxide dismutase (SOD1), the protein destabilized in the most common form of familial amyotrophic lateral sclerosis.
  Proc Natl Acad Sci U S A, 107, 21394-21399.  
20232802 R.J.Nowak, G.D.Cuny, S.Choi, P.T.Lansbury, and S.S.Ray (2010).
Improving binding specificity of pharmacological chaperones that target mutant superoxide dismutase-1 linked to familial amyotrophic lateral sclerosis using computational methods.
  J Med Chem, 53, 2709-2718.  
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
19063897 D.S.Shin, M.Didonato, D.P.Barondeau, G.L.Hura, C.Hitomi, J.A.Berglund, E.D.Getzoff, S.C.Cary, and J.A.Tainer (2009).
Superoxide dismutase from the eukaryotic thermophile Alvinella pompejana: structures, stability, mechanism, and insights into amyotrophic lateral sclerosis.
  J Mol Biol, 385, 1534-1555.
PDB codes: 3f7k 3f7l
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.  
19325915 Z.A.Oztug Durer, J.A.Cohlberg, P.Dinh, S.Padua, K.Ehrenclou, S.Downes, J.K.Tan, Y.Nakano, C.J.Bowman, J.L.Hoskins, C.Kwon, A.Z.Mason, J.A.Rodriguez, P.A.Doucette, B.F.Shaw, and J.Selverstone Valentine (2009).
Loss of metal ions, disulfide reduction and mutations related to familial ALS promote formation of amyloid-like aggregates from superoxide dismutase.
  PLoS ONE, 4, e5004.  
18840448 C.Kayatekin, J.A.Zitzewitz, and C.R.Matthews (2008).
Zinc binding modulates the entire folding free energy surface of human Cu,Zn superoxide dismutase.
  J Mol Biol, 384, 540-555.  
18634877 R.W.Strange, and M.C.Feiters (2008).
Biological X-ray absorption spectroscopy (BioXAS): a valuable tool for the study of trace elements in the life sciences.
  Curr Opin Struct Biol, 18, 609-616.  
18378676 X.Cao, S.V.Antonyuk, S.V.Seetharaman, L.J.Whitson, A.B.Taylor, S.P.Holloway, R.W.Strange, P.A.Doucette, J.S.Valentine, A.Tiwari, L.J.Hayward, S.Padua, J.A.Cohlberg, S.S.Hasnain, and P.J.Hart (2008).
Structures of the G85R variant of SOD1 in familial amyotrophic lateral sclerosis.
  J Biol Chem, 283, 16169-16177.
PDB codes: 2vr6 2vr7 2vr8 3cqp 3cqq
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
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.  
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.