PDBsum entry 1mfm

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protein metals links
Oxidoreductase PDB id
Protein chain
153 a.a. *
_CL ×2
_CD ×9
Waters ×283
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Monomeric human sod mutant f50e/g51e/e133q at atomic resolution
Structure: Protein (copper,zinc superoxide dismutase). Chain: a. Synonym: q133m2sod. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Cellular_location: cytoplasm. Gene: sod1. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.02Å     R-factor:   0.118    
Authors: M.Ferraroni,W.Rypniewski,K.S.Wilson,P.L.Orioli,M.S.Viezzoli, L.Banci,I.Bertini,S.Mangani
Key ref:
M.Ferraroni et al. (1999). The crystal structure of the monomeric human SOD mutant F50E/G51E/E133Q at atomic resolution. The enzyme mechanism revisited. J Mol Biol, 288, 413-426. PubMed id: 10329151 DOI: 10.1006/jmbi.1999.2681
16-Apr-99     Release date:   21-Apr-99    
Go to PROCHECK summary

Protein chain
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 5 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: Iron or manganese or (zinc and copper)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   15 terms 
  Biological process     reactive oxygen species metabolic process   62 terms 
  Biochemical function     antioxidant activity     12 terms  


    Added reference    
DOI no: 10.1006/jmbi.1999.2681 J Mol Biol 288:413-426 (1999)
PubMed id: 10329151  
The crystal structure of the monomeric human SOD mutant F50E/G51E/E133Q at atomic resolution. The enzyme mechanism revisited.
M.Ferraroni, W.Rypniewski, K.S.Wilson, M.S.Viezzoli, L.Banci, I.Bertini, S.Mangani.
The crystal structure of the engineered monomeric human Cu,ZnSOD triple mutant F50E/G51E/E133Q (Q133M2SOD) is reported at atomic resolution (1.02 A). This derivative has about 20 % of the wild-type activity. Crystals of Q133M2SOD have been obtained in the presence of CdCl2. The metal binding site is disordered, with both cadmium and copper ions simultaneously binding to the copper site. The cadmium (II) ions occupy about 45 % of the copper sites by binding the four histidine residues which ligate copper in the native enzyme, and two further water molecules to complete octahedral coordination. The copper ion is tri-coordinate, and the fourth histidine (His63) is detached from copper and bridges cadmium and zinc. X-ray absorption spectroscopy performed on the crystals suggests that the copper ion has undergone partial photoreduction upon exposure to the synchrotron light. The structure is also disordered in the disulfide bridge region of loop IV that is located at the subunit/subunit interface in the native SOD dimer. As a consequence, the catalytically relevant Arg143 residue is disordered. The present structure has been compared to other X-ray structures on various isoenzymes and to the solution structure of the same monomeric form. The structural results suggest that the low activity of monomeric SOD is due to the disorder in the conformation of the side-chain of Arg143 as well as of loop IV. It is proposed that the subunit-subunit interactions in the multimeric forms of the enzyme are needed to stabilize the correct geometry of the cavity and the optimal orientation of the charged residues in the active channel. Furthermore, the different coordination of cadmium and copper ions, contemporaneously present in the same site, are taken as models for the oxidized and reduced copper species, respectively. These properties of the structure have allowed us to revisit the enzymatic mechanism.
  Selected figure(s)  
Figure 1.
Figure 1. Schematic view of the Q133M2SOD structure displaying the secondary structure elements numbered by Getzoff et al. (1989). The side-chains of the residues homologous to those involved in the subunit-subunit interface in the WT dimer are shown as yellow sticks. The mutated residues E50, E51, Q133 are shown as red sticks. Orange, yellow and gray spheres of arbitrary radius represent copper, cadmium and zinc ions, respectively.
Figure 4.
Figure 4. The (a) cadmium and (b) copper sites shown by a 3F[o] − 2F[c] electron density map from the atomic resolution data set, contoured at 2σ (1.28 e^−·Å^−3) superimposed to the final model.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1999, 288, 413-426) copyright 1999.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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
19299510 K.C.Wilcox, L.Zhou, J.K.Jordon, Y.Huang, Y.Yu, R.L.Redler, X.Chen, M.Caplow, and N.V.Dokholyan (2009).
Modifications of superoxide dismutase (SOD1) in human erythrocytes: a possible role in amyotrophic lateral sclerosis.
  J Biol Chem, 284, 13940-13947.  
18645235 C.Dumas, and A.van der Lee (2008).
Macromolecular structure solution by charge flipping.
  Acta Crystallogr D Biol Crystallogr, 64, 864-873.  
17041047 A.Dryla, B.Hoffmann, D.Gelbmann, C.Giefing, M.Hanner, A.Meinke, A.S.Anderson, W.Koppensteiner, R.Konrat, A.von Gabain, and E.Nagy (2007).
High-affinity binding of the staphylococcal HarA protein to haptoglobin and hemoglobin involves a domain with an antiparallel eight-stranded beta-barrel fold.
  J Bacteriol, 189, 254-264.  
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
17623850 B.Tamames, S.F.Sousa, J.Tamames, P.A.Fernandes, and M.J.Ramos (2007).
Analysis of zinc-ligand bond lengths in metalloproteins: trends and patterns.
  Proteins, 69, 466-475.  
16420476 L.Villarreal, L.Tío, M.Capdevila, and S.Atrian (2006).
Comparative metal binding and genomic analysis of the avian (chicken) and mammalian metallothionein.
  FEBS J, 273, 523-535.  
17107883 S.D.Khare, M.Caplow, and N.V.Dokholyan (2006).
FALS mutations in Cu, Zn superoxide dismutase destabilize the dimer and increase dimer dissociation propensity: a large-scale thermodynamic analysis.
  Amyloid, 13, 226-235.  
16488975 S.D.Khare, and N.V.Dokholyan (2006).
Common dynamical signatures of familial amyotrophic lateral sclerosis-associated structurally diverse Cu, Zn superoxide dismutase mutants.
  Proc Natl Acad Sci U S A, 103, 3147-3152.  
15952898 J.S.Valentine, P.A.Doucette, and S.Zittin Potter (2005).
Copper-zinc superoxide dismutase and amyotrophic lateral sclerosis.
  Annu Rev Biochem, 74, 563-593.  
15987780 M.J.Lindberg, R.Byström, N.Boknäs, P.M.Andersen, and M.Oliveberg (2005).
Systematically perturbed folding patterns of amyotrophic lateral sclerosis (ALS)-associated SOD1 mutants.
  Proc Natl Acad Sci U S A, 102, 9754-9759.  
15817398 O.Carugo, and K.Djinović Carugo (2005).
When X-rays modify the protein structure: radiation damage at work.
  Trends Biochem Sci, 30, 213-219.  
15522970 M.J.Lindberg, J.Normark, A.Holmgren, and M.Oliveberg (2004).
Folding of human superoxide dismutase: disulfide reduction prevents dimerization and produces marginally stable monomers.
  Proc Natl Acad Sci U S A, 101, 15893-15898.  
15485869 P.A.Doucette, L.J.Whitson, X.Cao, V.Schirf, B.Demeler, J.S.Valentine, J.C.Hansen, and P.J.Hart (2004).
Dissociation of human copper-zinc superoxide dismutase dimers using chaotrope and reductant. Insights into the molecular basis for dimer stability.
  J Biol Chem, 279, 54558-54566.  
12957544 R.E.Steward, M.W.MacArthur, R.A.Laskowski, and J.M.Thornton (2003).
Molecular basis of inherited diseases: a structural perspective.
  Trends Genet, 19, 505-513.  
12237469 L.Banci, I.Bertini, F.Cantini, M.D'Onofrio, and M.S.Viezzoli (2002).
Structure and dynamics of copper-free SOD: The protein before binding copper.
  Protein Sci, 11, 2479-2492.
PDB code: 1kmg
11952792 L.Banci, I.Bertini, F.Cramaro, R.Del Conte, and M.S.Viezzoli (2002).
The solution structure of reduced dimeric copper zinc superoxide dismutase. The structural effects of dimerization.
  Eur J Biochem, 269, 1905-1915.
PDB code: 1l3n
11863429 L.Banci, I.C.Felli, and R.Kümmerle (2002).
Direct detection of hydrogen bonds in monomeric superoxide dismutase: biological implications.
  Biochemistry, 41, 2913-2920.  
11679732 W.Liu, P.W.Li, G.P.Li, R.H.Zhu, and D.C.Wang (2001).
Overexpression, purification, crystallization and preliminary X-ray diffraction analysis of Cu,Zn superoxide dismutase from Peking duck.
  Acta Crystallogr D Biol Crystallogr, 57, 1646-1649.  
10704199 A.P.Yeh, Y.Hu, F.E.Jenney, M.W.Adams, and D.C.Rees (2000).
Structures of the superoxide reductase from Pyrococcus furiosus in the oxidized and reduced states.
  Biochemistry, 39, 2499-2508.
PDB codes: 1do6 1dqi 1dqk
10924104 L.Banci, I.Bertini, F.Cramaro, R.Del Conte, A.Rosato, and M.S.Viezzoli (2000).
Backbone dynamics of human Cu,Zn superoxide dismutase and of its monomeric F50E/G51E/E133Q mutant: the influence of dimerization on mobility and function.
  Biochemistry, 39, 9108-9118.  
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.