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PDBsum entry 2gbv

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protein metals Protein-protein interface(s) links
Oxidoreductase PDB id
2gbv
Jmol
Contents
Protein chain
(+ 4 more) 153 a.a. *
Metals
_ZN ×10
CU1 ×10
Waters ×1498
* Residue conservation analysis
PDB id:
2gbv
Name: Oxidoreductase
Title: C6a/c111a/c57a/c146a holo cuzn superoxide dismutase
Structure: Superoxide dismutase [cu-zn]. Chain: a, b, c, d, e, f, g, h, i, j. Synonym: cu/zn superoxide dismutase. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: sod1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
2.00Å     R-factor:   0.184     R-free:   0.207
Authors: A.Hornberg,D.T.Logan,S.L.Marklund,M.Oliveberg
Key ref:
A.Hörnberg et al. (2007). The coupling between disulphide status, metallation and dimer interface strength in Cu/Zn superoxide dismutase. J Mol Biol, 365, 333-342. PubMed id: 17070542 DOI: 10.1016/j.jmb.2006.09.048
Date:
11-Mar-06     Release date:   02-Jan-07    
PROCHECK
Go to PROCHECK summary
 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 4 residue positions (black crosses)

 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   20 terms 
  Biological process     cellular response to potassium ion   66 terms 
  Biochemical function     antioxidant activity     13 terms  

 

 
    Added reference    
 
 
DOI no: 10.1016/j.jmb.2006.09.048 J Mol Biol 365:333-342 (2007)
PubMed id: 17070542  
 
 
The coupling between disulphide status, metallation and dimer interface strength in Cu/Zn superoxide dismutase.
A.Hörnberg, D.T.Logan, S.L.Marklund, M.Oliveberg.
 
  ABSTRACT  
 
The gain of neurotoxic function in amyotrophic lateral sclerosis (ALS) has been linked to misfolding of the homodimeric enzyme Cu/Zn superoxide dismutase (SOD). Here, we present the crystal structure of fully cysteine-depleted human SOD (SOD(CallA)), representing a reduced, marginally stable intermediate on the folding pathway in vivo that has also been implicated as neurotoxic precursor state. A hallmark of this species is that it fails to dimerize and becomes trapped as a monomer in the absence of the active-site metals. The crystallographic data show that removal of the C57-C146 disulphide bond sets free the interface loop IV in the apo protein, whereas the same loop remains unaffected in the holo protein. Thus, the low dimerisation propensity of disulphide-reduced apoSOD seems to be of entropic origin due to increased loop flexibility in the monomeric state: in the disulphide-reduced holo protein this gain in configurational entropy upon splitting of the dimer interface is reduced by the metal coordination.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. Changes of the homodimer interface of the fully cysteine-depleted variant apoSOD^CallA. (a) The apoSOD^CallA dimer. (b) The interface areas of the individual apoSOD^CallA monomers indicating the contacts that are lost, weakened and maintained upon truncation of the C57–C146 disulphide link and movement of loop IV. Figure 3. Changes of the homodimer interface of the fully cysteine-depleted variant apoSOD^CallA. (a) The apoSOD^CallA dimer. (b) The interface areas of the individual apoSOD^CallA monomers indicating the contacts that are lost, weakened and maintained upon truncation of the C57–C146 disulphide link and movement of loop IV.
Figure 4.
Figure 4. Displacement of Arg143 in apoSOD^CallA provides a clue to the structural origin of decreased activity in monomeric and disulphide-reduced protein. Accompanying the structural alteration of loop IV, the catalytically important guanidinium group of R143 moves from its native position and forms new hydrogen bonds with S59, D52 and the water molecules Wat26 and Wat68. (a) The 2F[o]–F[c] electron density map of apoSOD^CallA at 1σ. (b) Schematic representation of the apoSOD^CallA structure illustrating the hydrogen bonding to R143. (c) Comparison of the loop IV conformations and positioning of R143 by superposition of the A monomers of apoSOD^CallA (blue) and holoSOD^CallA (red). Figure 4. Displacement of Arg143 in apoSOD^CallA provides a clue to the structural origin of decreased activity in monomeric and disulphide-reduced protein. Accompanying the structural alteration of loop IV, the catalytically important guanidinium group of R143 moves from its native position and forms new hydrogen bonds with S59, D52 and the water molecules Wat26 and Wat68. (a) The 2F[o]–F[c] electron density map of apoSOD^CallA at 1σ. (b) Schematic representation of the apoSOD^CallA structure illustrating the hydrogen bonding to R143. (c) Comparison of the loop IV conformations and positioning of R143 by superposition of the A monomers of apoSOD^CallA (blue) and holoSOD^CallA (red).
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2007, 365, 333-342) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21396374 E.A.Proctor, F.Ding, and N.V.Dokholyan (2011).
Structural and thermodynamic effects of post-translational modifications in mutant and wild type Cu, Zn superoxide dismutase.
  J Mol Biol, 408, 555-567.  
21078595 L.R.Fischer, A.Igoudjil, J.Magrané, Y.Li, J.M.Hansen, G.Manfredi, and J.D.Glass (2011).
SOD1 targeted to the mitochondrial intermembrane space prevents motor neuropathy in the Sod1 knockout mouse.
  Brain, 134, 196-209.  
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.  
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.  
19497878 A.Nordlund, L.Leinartaite, K.Saraboji, C.Aisenbrey, G.Gröbner, P.Zetterström, J.Danielsson, D.T.Logan, and M.Oliveberg (2009).
Functional features cause misfolding of the ALS-provoking enzyme SOD1.
  Proc Natl Acad Sci U S A, 106, 9667-9672.
PDB code: 3hff
19651777 A.Tiwari, A.Liba, S.H.Sohn, S.V.Seetharaman, O.Bilsel, C.R.Matthews, P.J.Hart, J.S.Valentine, and L.J.Hayward (2009).
Metal deficiency increases aberrant hydrophobicity of mutant superoxide dismutases that cause amyotrophic lateral sclerosis.
  J Biol Chem, 284, 27746-27758.  
19542232 J.M.Leitch, L.T.Jensen, S.D.Bouldin, C.E.Outten, P.J.Hart, and V.C.Culotta (2009).
Activation of Cu,Zn-superoxide dismutase in the absence of oxygen and the copper chaperone CCS.
  J Biol Chem, 284, 21863-21871.  
19309264 K.A.Trumbull, and J.S.Beckman (2009).
A role for copper in the toxicity of zinc-deficient superoxide dismutase to motor neurons in amyotrophic lateral sclerosis.
  Antioxid Redox Signal, 11, 1627-1639.  
19436494 A.Nordlund, and M.Oliveberg (2008).
SOD1-associated ALS: a promising system for elucidating the origin of protein-misfolding disease.
  HFSP J, 2, 354-364.  
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.  
19052230 F.Ding, and N.V.Dokholyan (2008).
Dynamical roles of metal ions and the disulfide bond in Cu, Zn superoxide dismutase folding and aggregation.
  Proc Natl Acad Sci U S A, 105, 19696-19701.  
18703498 H.Kawamata, and G.Manfredi (2008).
Different regulation of wild-type and mutant Cu,Zn superoxide dismutase localization in mammalian mitochondria.
  Hum Mol Genet, 17, 3303-3317.  
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
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 code is shown on the right.