PDBsum entry 1em1

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
Protein chains
198 a.a. *
SO4 ×2
_MN ×2
Waters ×293
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: X-ray crystal structure for human manganese superoxide dismu q143a
Structure: Manganese superoxide dismutase. Chain: a, b. Synonym: hmnsod. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Organelle: mitochondria. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PDB file)
2.13Å     R-factor:   0.232     R-free:   0.264
Authors: V.Leveque,M.E.Stroupe,J.R.Lepock,D.E.Cabelli,J.A.Tainer,H.S. D.N.Silverman
Key ref:
V.J.Lévêque et al. (2000). Multiple replacements of glutamine 143 in human manganese superoxide dismutase: effects on structure, stability, and catalysis. Biochemistry, 39, 7131-7137. PubMed id: 10852710 DOI: 10.1021/bi9929958
14-Mar-00     Release date:   24-Mar-00    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P04179  (SODM_HUMAN) -  Superoxide dismutase [Mn], mitochondrial
222 a.a.
198 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.  - 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!
  Biological process     oxidation-reduction process   2 terms 
  Biochemical function     superoxide dismutase activity     2 terms  


    Added reference    
DOI no: 10.1021/bi9929958 Biochemistry 39:7131-7137 (2000)
PubMed id: 10852710  
Multiple replacements of glutamine 143 in human manganese superoxide dismutase: effects on structure, stability, and catalysis.
V.J.Lévêque, M.E.Stroupe, J.R.Lepock, D.E.Cabelli, J.A.Tainer, H.S.Nick, D.N.Silverman.
Glutamine 143 in human manganese superoxide dismutase (MnSOD) forms a hydrogen bond with the manganese-bound solvent molecule and is investigated by replacement using site-specific mutagenesis. Crystal structures showed that the replacement of Gln 143 with Ala made no significant change in the overall structure of the mutant enzyme. Two new water molecules in Q143A MnSOD were situated in positions nearly identical with the Oepsilon1 and Nepsilon2 of the replaced Gln 143 side chain and maintained a hydrogen-bonded network connecting the manganese-bound solvent molecule to other residues in the active site. However, their presence could not sustain the stability and activity of the enzyme; the main unfolding transition of Q143A was decreased 16 degrees C and its catalysis decreased 250-fold to k(cat)/K(m) = 3 x 10(6) M(-)(1) s(-)(1), as determined by stopped-flow spectrophotometry and pulse radiolysis. The mutant Q143A MnSOD and other mutants at position 143 showed very low levels of product inhibition and favored Mn(II)SOD in the resting state, whereas the wild type showed strong product inhibition and favored Mn(III)SOD. However, these differences did not affect the rate constant for dissociation of the product-inhibited complex in Q143A MnSOD which was determined from a characteristic absorbance at 420 nm and was comparable in magnitude ( approximately 100 s(-)(1)) to that of the wild-type enzyme. Hence, Gln 143, which is necessary for maximal activity in superoxide dismutation, appears to have no role in stabilization and dissociation of the product-inhibited complex.

Literature references that cite this PDB file's key reference

  PubMed id Reference
19384983 I.Castellano, F.Cecere, A.De Vendittis, R.Cotugno, A.Chambery, A.Di Maro, A.Michniewicz, G.Parlato, M.Masullo, E.V.Avvedimento, E.De Vendittis, and M.R.Ruocco (2009).
Rat mitochondrial manganese superoxide dismutase: Amino acid positions involved in covalent modifications, activity, and heat stability.
  Biopolymers, 91, 1215-1226.  
19265433 J.J.Perry, A.S.Hearn, D.E.Cabelli, H.S.Nick, J.A.Tainer, and D.N.Silverman (2009).
Contribution of human manganese superoxide dismutase tyrosine 34 to structure and catalysis.
  Biochemistry, 48, 3417-3424.
PDB codes: 1zsp 1zte 1zuq 2p4k
17912757 R.Wintjens, D.Gilis, and M.Rooman (2008).
Mn/Fe superoxide dismutase interaction fingerprints and prediction of oligomerization and metal cofactor from sequence.
  Proteins, 70, 1564-1577.  
18335973 V.M.Krishnamurthy, G.K.Kaufman, A.R.Urbach, I.Gitlin, K.L.Gudiksen, D.B.Weibel, and G.M.Whitesides (2008).
Carbonic anhydrase as a model for biophysical and physical-organic studies of proteins and protein-ligand binding.
  Chem Rev, 108, 946.  
17174478 J.J.Perry, L.Fan, and J.A.Tainer (2007).
Developing master keys to brain pathology, cancer and aging from the structural biology of proteins controlling reactive oxygen species and DNA repair.
  Neuroscience, 145, 1280-1299.  
16999822 K.Chockalingam, J.Luba, H.S.Nick, D.N.Silverman, and H.Zhao (2006).
Engineering and characterization of human manganese superoxide dismutase mutants with high activity and low product inhibition.
  FEBS J, 273, 4853-4861.  
15851472 E.Luk, M.Yang, L.T.Jensen, Y.Bourbonnais, and V.C.Culotta (2005).
Manganese activation of superoxide dismutase 2 in the mitochondria of Saccharomyces cerevisiae.
  J Biol Chem, 280, 22715-22720.  
14672935 R.Wintjens, C.Noël, A.C.May, D.Gerbod, F.Dufernez, M.Capron, E.Viscogliosi, and M.Rooman (2004).
Specificity and phenetic relationships of iron- and manganese-containing superoxide dismutases on the basis of structure and sequence comparisons.
  J Biol Chem, 279, 9248-9254.  
12890866 E.Luk, M.Carroll, M.Baker, and V.C.Culotta (2003).
Manganese activation of superoxide dismutase 2 in Saccharomyces cerevisiae requires MTM1, a member of the mitochondrial carrier family.
  Proc Natl Acad Sci U S A, 100, 10353-10357.  
12730184 L.C.Tabares, C.Bittel, N.Carrillo, A.Bortolotti, and N.Cortez (2003).
The single superoxide dismutase of Rhodobacter capsulatus is a cambialistic, manganese-containing enzyme.
  J Bacteriol, 185, 3223-3227.  
12392545 T.Hunter, J.V.Bannister, and G.J.Hunter (2002).
Thermostability of manganese- and iron-superoxide dismutases from Escherichia coli is determined by the characteristic position of a glutamine residue.
  Eur J Biochem, 269, 5137-5148.  
11141052 R.A.Edwards, M.M.Whittaker, J.W.Whittaker, E.N.Baker, and G.B.Jameson (2001).
Outer sphere mutations perturb metal reactivity in manganese superoxide dismutase.
  Biochemistry, 40, 15-27.
PDB codes: 1en4 1en5 1en6
11294629 R.A.Edwards, M.M.Whittaker, J.W.Whittaker, E.N.Baker, and G.B.Jameson (2001).
Removing a hydrogen bond in the dimer interface of Escherichia coli manganese superoxide dismutase alters structure and reactivity.
  Biochemistry, 40, 4622-4632.
PDB codes: 1i08 1i0h
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 codes are shown on the right.