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Oxidoreductase PDB id
Protein chain
(+ 4 more) 153 a.a. *
_ZN ×10
_CU ×10
Waters ×239
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Superoxide dismutase mutant with lys 136 replaced by glu, cys 6 replaced by ala and cys 111 replaced by ser (k136e, c6a, c111s)
Structure: Superoxide dismutase. Chain: a, f, b, g, c, h, d, i, e, j. Synonym: sod. Engineered: yes. Mutation: yes. Other_details: five biological dimers are present in the crystallographic asymmetric unit. They are a and f, b and g, c and h, d and i, e and j.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Homo-Dimer (from PDB file)
2.85Å     R-factor:   0.189    
Authors: T.P.Lo,J.A.Tainer,E.D.Getzoff
Key ref: C.L.Fisher et al. (1997). Computational, pulse-radiolytic, and structural investigations of lysine-136 and its role in the electrostatic triad of human Cu,Zn superoxide dismutase. Proteins, 29, 103-112. PubMed id: 9294870
23-Jul-98     Release date:   23-Jul-99    
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 3 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   20 terms 
  Biological process     cellular response to potassium ion   66 terms 
  Biochemical function     antioxidant activity     13 terms  


    Added reference    
Proteins 29:103-112 (1997)
PubMed id: 9294870  
Computational, pulse-radiolytic, and structural investigations of lysine-136 and its role in the electrostatic triad of human Cu,Zn superoxide dismutase.
C.L.Fisher, D.E.Cabelli, R.A.Hallewell, P.Beroza, T.P.Lo, E.D.Getzoff, J.A.Tainer.
Key charged residues in Cu,Zn superoxide dismutase (Cu,Zn SOD) promote electrostatic steering of the superoxide substrate to the active site Cu ion, resulting in dismutation of superoxide to oxygen and hydrogen peroxide, Lys-136, along with the adjacent residues Glu-132 and Glu-133, forms a proposed electrostatic triad contributing to substrate recognition. Human Cu,Zn SODs with single-site replacements of Lys-136 by Arg,Ala, Gln, or Glu or with a triple-site substitution (Glu-132 and Glu-133 to Gln and Lys-136 to Ala) were made to test hypotheses regarding contributions of these residues to Cu,Zn SOD activity. The structural effects of these mutations were modeled computationally and validated by the X-ray crystallographic structure determination of Cu,Zn SOD having the Lys-136-to-Glu replacement. Brownian dynamics simulations and multiple-site titration calculations predicted mutant reaction rates as well as ionic strength and pH effects measured by pulse-radiolytic experiments. Lys-136-to-Glu charge reversal decreased dismutation activity 50% from 2.2 x 10(9) to 1.2 x 10(9) M-1 s-1 due to repulsion of negatively charged superoxide, whereas charge-neutralizing substitutions (Lys-136 to Gln or Ala) had a less dramatic influence. In contrast, the triple-mutant Cu,Zn SOD (all three charges in the electrostatic triad neutralized) surprisingly doubled the reaction rate compared with wild-type enzyme but introduced phosphate inhibition. Computational and experimental reaction rates decreased with increasing ionic strength in all of the Lys-136 mutants, with charge reversal having a more pronounced effect than charge neutralization, implying that local electrostatic effects still govern the dismutation rates. Multiple-site titration analysis showed that deprotonation events throughout the enzyme are likely responsible for the gradual decrease in SOD activity above pH 9.5 and predicted a pKa value of 11.7 for Lys-136. Overall, Lys-136 and Glu-132 make comparable contributions to substrate recognition but are less critical to enzyme function than Arg-143, which is both mechanistically and electrostatically essential. Thus, the sequence-conserved residues of this electrostatic triad are evidently important solely for their electrostatic properties, which maintain the high catalytic rate and turnover of Cu,Zn SOD while simultaneously providing specificity by selecting against binding by other anions.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20333421 K.C.Ryan, O.E.Johnson, D.E.Cabelli, T.C.Brunold, and M.J.Maroney (2010).
Nickel superoxide dismutase: structural and functional roles of Cys2 and Cys6.
  J Biol Inorg Chem, 15, 795-807.  
10677207 A.L.Lamb, A.K.Wernimont, R.A.Pufahl, T.V.O'Halloran, and A.C.Rosenzweig (2000).
Crystal structure of the second domain of the human copper chaperone for superoxide dismutase.
  Biochemistry, 39, 1589-1595.
PDB code: 1do5
10920003 A.Rojnuckarin, D.R.Livesay, and S.Subramaniam (2000).
Bimolecular reaction simulation using Weighted Ensemble Brownian dynamics and the University of Houston Brownian Dynamics program.
  Biophys J, 79, 686-693.  
9631295 A.Warshel, and A.Papazyan (1998).
Electrostatic effects in macromolecules: fundamental concepts and practical modeling.
  Curr Opin Struct Biol, 8, 211-217.  
  9828001 F.Polticelli, A.Battistoni, P.O'Neill, G.Rotilio, and A.Desideri (1998).
Role of the electrostatic loop charged residues in Cu,Zn superoxide dismutase.
  Protein Sci, 7, 2354-2358.  
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.