PDBsum entry 3gqf

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protein metals Protein-protein interface(s) links
Oxidoreductase PDB id
Protein chain
(+ 0 more) 153 a.a. *
_CA ×5
_ZN ×6
Waters ×498
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Structural and biophysical properties of the pathogenic sod1 variant h46r/h48q
Structure: Superoxide dismutase [cu-zn]. Chain: a, b, c, d, e, f. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: sod1. Expressed in: saccharomyces cerevisiae. Expression_system_taxid: 4932.
2.20Å     R-factor:   0.207     R-free:   0.242
Authors: D.D.Winkler,J.P.Schuermann,P.J.Hart
Key ref: D.D.Winkler et al. (2009). Structural and biophysical properties of the pathogenic SOD1 variant H46R/H48Q. Biochemistry, 48, 3436-3447. PubMed id: 19227972
24-Mar-09     Release date:   07-Apr-09    
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   17 terms 
  Biological process     reactive oxygen species metabolic process   60 terms 
  Biochemical function     antioxidant activity     12 terms  


    Added reference    
Biochemistry 48:3436-3447 (2009)
PubMed id: 19227972  
Structural and biophysical properties of the pathogenic SOD1 variant H46R/H48Q.
D.D.Winkler, J.P.Schuermann, X.Cao, S.P.Holloway, D.R.Borchelt, M.C.Carroll, J.B.Proescher, V.C.Culotta, P.J.Hart.
Over 100 mutations in the gene encoding human copper-zinc superoxide dismutase (SOD1) cause an inherited form of the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS). Two pathogenic SOD1 mutations, His46Arg (H46R) and His48Gln (H48Q), affect residues that act as copper ligands in the wild type enzyme. Transgenic mice expressing a human SOD1 variant containing both mutations develop paralytic disease akin to ALS. Here we show that H46R/H48Q SOD1 possesses multiple characteristics that distinguish it from the wild type. These properties include the following: (1) an ablated copper-binding site, (2) a substantially weakened affinity for zinc, (3) a binding site for a calcium ion, (4) the ability to form stable heterocomplexes with the copper chaperone for SOD1 (CCS), and (5) compromised CCS-mediated oxidation of the intrasubunit disulfide bond in vivo. The results presented here, together with data on pathogenic SOD1 proteins coming from cell culture and transgenic mice, suggest that incomplete posttranslational modification of nascent SOD1 polypeptides via CCS may be a characteristic shared by familial ALS SOD1 mutants, leading to a population of destabilized, off-pathway folding intermediates that are toxic to motor neurons.

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
20205585 N.J.Robinson, and D.R.Winge (2010).
Copper metallochaperones.
  Annu Rev Biochem, 79, 537-562.  
20052996 Z.You, X.Cao, A.B.Taylor, P.J.Hart, and R.L.Levine (2010).
Characterization of a covalent polysulfane bridge in copper-zinc superoxide dismutase .
  Biochemistry, 49, 1191-1198.
PDB code: 3k91
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.  
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