PDBsum entry 4a7t

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
Protein chain
153 a.a.
5FW ×5
SO4 ×4
ACT ×2
_ZN ×2
_CU ×2
Waters ×372
PDB id:
Name: Oxidoreductase
Title: Structure of human i113t sod1 mutant complexed with isoproteranol in the p21 space group
Structure: Superoxide dismutase [cu-zn]. Chain: a, f. Synonym: superoxide dismutase-1, superoxide dismutase 1, hs engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008.
1.45Å     R-factor:   0.158     R-free:   0.187
Authors: G.S.A.Wright,S.V.Antonyuk,N.M.Kershaw,R.W.Strange,S.S.Hasnai
Key ref: G.S.Wright et al. (2013). Ligand binding and aggregation of pathogenic SOD1. Nat Commun, 4, 1758. PubMed id: 23612299 DOI: 10.1038/ncomms2750
14-Nov-11     Release date:   28-Nov-12    
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 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     extracellular region   20 terms 
  Biological process     cellular response to potassium ion   66 terms 
  Biochemical function     antioxidant activity     13 terms  


    Added reference    
DOI no: 10.1038/ncomms2750 Nat Commun 4:1758 (2013)
PubMed id: 23612299  
Ligand binding and aggregation of pathogenic SOD1.
G.S.Wright, S.V.Antonyuk, N.M.Kershaw, R.W.Strange, S.Samar Hasnain.
Mutations in the gene encoding Cu/Zn superoxide dismutase-1 cause amyotrophic lateral sclerosis. Superoxide dismutase-1 mutations decrease protein stability and promote aggregation. The mutant monomer is thought to be an intermediate in the pathway from the superoxide dismutase-1 dimer to aggregate. Here we find that the monomeric copper-apo, zinc-holo protein is structurally perturbed and the apo-protein aggregates without reattainment of the monomer-dimer equilibrium. Intervention to stabilize the superoxide dismutase-1 dimer and inhibit aggregation is regarded as a potential therapeutic strategy. We describe protein-ligand interactions for two compounds, Isoproterenol and 5-fluorouridine, highlighted as superoxide dismutase-1 stabilizers. We find both compounds interact with superoxide dismutase-1 at a key region identified at the core of the superoxide dismutase-1 fibrillar aggregates, β-barrel loop II-strand 3, rather than the proposed dimer interface site. This illustrates the need for direct structural observations when developing compounds for protein-targeted therapeutics.