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PDBsum entry 4a7u

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
4a7u
Jmol
Contents
Protein chain
153 a.a.
Ligands
ALE ×2
SO4 ×4
ACT
Metals
_ZN ×2
_CU ×2
Waters ×283
PDB id:
4a7u
Name: Oxidoreductase
Title: Structure of human i113t sod1 complexed with adrenaline 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.
Resolution:
0.98Å     R-factor:   0.138     R-free:   0.153
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
Date:
14-Nov-11     Release date:   28-Nov-12    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P00441  (SODC_HUMAN) -  Superoxide dismutase [Cu-Zn]
Seq:
Struc:
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.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
 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: 10.1038/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.
 
  ABSTRACT  
 
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.