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PDBsum entry 2jlp

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
2jlp
Jmol
Contents
Protein chains
168 a.a. *
Ligands
SCN ×2
Metals
_ZN ×4
_CU ×4
Waters ×889
* Residue conservation analysis
PDB id:
2jlp
Name: Oxidoreductase
Title: Crystal structure of human extracellular copper-zinc superoxide dismutase.
Structure: Extracellular superoxide dismutase (cu-zn). Chain: a, b, c, d. Synonym: extracellular copper-zinc superoxide dismutase, ec engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_cell_line: cho cells. Expression_system_tissue: ovary
Resolution:
1.70Å     R-factor:   0.152     R-free:   0.185
Authors: S.V.Antonyuk,R.W.Strange,S.L.Marklund,S.S.Hasnain
Key ref:
S.V.Antonyuk et al. (2009). The structure of human extracellular copper-zinc superoxide dismutase at 1.7 A resolution: insights into heparin and collagen binding. J Mol Biol, 388, 310-326. PubMed id: 19289127 DOI: 10.1016/j.jmb.2009.03.026
Date:
14-Sep-08     Release date:   17-Mar-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P08294  (SODE_HUMAN) -  Extracellular superoxide dismutase [Cu-Zn]
Seq:
Struc:
240 a.a.
168 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   8 terms 
  Biological process     oxidation-reduction process   5 terms 
  Biochemical function     antioxidant activity     8 terms  

 

 
    Added reference    
 
 
DOI no: 10.1016/j.jmb.2009.03.026 J Mol Biol 388:310-326 (2009)
PubMed id: 19289127  
 
 
The structure of human extracellular copper-zinc superoxide dismutase at 1.7 A resolution: insights into heparin and collagen binding.
S.V.Antonyuk, R.W.Strange, S.L.Marklund, S.S.Hasnain.
 
  ABSTRACT  
 
Extracellular superoxide dismutase (SOD3) is a homotetrameric copper- and zinc-containing glycoprotein with affinity for heparin. The level of SOD3 is particularly high in blood vessel walls and in the lungs. The enzyme has multiple roles including protection of the lungs against hyperoxia and preservation of nitric oxide. The common mutation R213G, which reduces the heparin affinity of SOD3, is associated with increased risk of myocardial infarctions and stroke. We report the first crystal structure of human SOD3 at 1.7 A resolution. The overall subunit fold and the subunit-subunit interface of the SOD3 dimer are similar to the corresponding structures in Cu-Zn SOD (SOD1). The metal-binding sites are similar to those found in SOD1, but with Asn180 replacing Thr137 at the Cu-binding site and a much shorter loop at the zinc-binding site. The dimers form a functional homotetramer that is fashioned through contacts between two extended loops on each subunit. The N- and C-terminal end regions required for tetramerisation and heparin binding, respectively, are highly flexible. Two grooves fashioned by the tetramer interface are suggestive as the probable sites for heparin and collagen binding.
 
  Selected figure(s)  
 
Figure 3.
Fig. 3. The 2F[o] − F[c] electron density maps contoured at 3σ at the Cu–Zn site of SOD3. The copper site contains two metal components corresponding to either oxidized or reduced fractions. (a) In subunits A and D, the oxidized Cu atom fraction (30%) possesses four histidine ligands and a water ligand, while the other component (70%) is due to reduced copper. The electron density map shows that the Cu(II)–His133–Zn bridge is intact, with a Cu(II)–His113 separation of 2.3–2.5 Å, while the distance from Cu and the nearest water molecule is 2.4–2.6 Å. The Cu(I) atom has only three histidine ligands and the Cu(I)–His113 separation is 3.1 and 3.2 Å, with no continuous electron density to the copper atom; (b) the water network at the active site of subunit A. Water molecule W1 is coordinated at 2.4 Å to the Cu(II) atom and at 3.7 Å distance from the Cu(I) atom component; (c) in subunits B and C the Cu–Zn site contains a fraction of copper sites with Cu coordinated to thiocyanate and a fraction without this ligand. The electron density maps show that the Cu–His133–Zn bridge is broken and that the Cu atom has only three histidine ligands, both indicative of the Cu(I) state. The change in the water network on thiocyanate binding is also shown; (d) a superposition of the active sites of SOD3 subunit A (green) and human SOD1 (red).^34 The metal ligands are numbered according to the SOD3 sequence. The copper-binding sites of the two proteins are in good spatial agreement, including the positions of the oxidized and reduced Cu atoms. The zinc-binding site protein residues shows larger positional differences that can be attributed to the truncated Zn-binding loop IV in the SOD3 structure relative to SOD1.
Figure 5.
Fig. 5. Simulated docking models of heparin and collagen binding to SOD3. (a) Stereo views of the SOD3 molecular surfaces for subunits A (red), B (yellow), C (blue), and D (green) are shown looking toward the base of the major groove (top) and toward the base of the minor groove (bottom). These views illustrate the locations of the two grooves on the opposite faces of the tetramer, while the middle panel shows an intermediate molecular orientation. In the top panel, the top 5 docking solutions for a dodecasaccharide heparin molecule are shown using different coloured spheres, while the preferred docking location of a synthetic collagen triple helix (pale blue spheres) is shown in the bottom panel; (b) surface representation highlighting the heparin-binding contact regions (< 4 Å) predicted by the docking calculations. The main contact areas for subunits A and D (pink) are on the extended loop III (Glu82, Phe84, Pro85, Thr86, and Glu87), β-strand 6 (Asp135 and Gly136), and the C-terminal helix (Arg202). The main contact areas for subunits B and C (magenta) are on the main tetrameric interface loop I (Ala51 and Thr52), the Zn-binding loop IV (Gln105, Glu108, Ser109, Thr110, Gly111, and Pro112) and electrostatic loop VII (Gln175, Ala176, Glu179, Arg185, and Arg186). The sites of N-glycosylation at Asn89 are located at the protein surface close to the major and minor grooves (cyan), with side chains exposed to solvent and accessible to glycosylation. The main surfaces of the protein that are in contact with the collagen molecule belong to loop I of each subunit and loop III of subunits B and C. The truncated C-terminal helices of these subunits are oriented toward each other across the minor groove and are suitably positioned to interact with the collagen molecule (not shown).
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2009, 388, 310-326) copyright 2009.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19716833 Q.Zhang, J.Pi, C.G.Woods, and M.E.Andersen (2010).
A systems biology perspective on Nrf2-mediated antioxidant response.
  Toxicol Appl Pharmacol, 244, 84-97.  
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