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Last modified: 11 January 1999

Mn-superoxide dismutase
Mononuclear manganese centre Manganese ligands Formal manganese
oxidation/spin states
Mn-SOD Mn centre

Mn(NepsilonHis)3OdeltaAspH2O
3 × NepsilonHis;

eta1­OdeltaAsp;

H2O or OH¯

MnII (S = 5/2);

MnIII (S = 2)

Superoxide dismutases (SODs) are antioxidant metalloenzymes catalysing the redox disproportionatin (dismutation) of superoxide radical, O2·¯ (1):

It is generally accepted that in all SODs the metal ion (M) catalyses dismutation of the superoxide radical through a cyclic oxidation­reduction mechanism: Four classes of SODs are known, distinguished by the metal prosthetic group: Cu/Zn, Fe, Mn and Ni. Fe­ and Mn-SODs constitute a structural family [1, 2]. Fe­ and Mn-SODs are unequally distributed throughout the kingdoms of living organisms and are located in different cellular compartments [3]. In particular, Mn-SOD is found in facultative aerobes (exclusively or together with Fe-SOD), in the thylakoid membranes of cyanobacteria and the chloroplasts of higher plants, and in mitochondria of higher plants, fungi and animals (cf. Fe-SOD). Fe-SOD and Mn-SOD from some organisms (e.g. Escherichia coli) exhibit almost absolute metal specificity [4], while other enzymes, such as `cambialistic' SOD from Propionibacterium shermanii, are active with either metal [5]. Fe­ and Mn-SODs occur as homodimers or homotetramers.

The 3­D structures of several Mn-SODs have been determined [6-9]. The monomers fold into two domains. The N­terminal domain consists of two long antiparallel alpha­helices. The C­terminal domain contains a central ß­sheet formed by three antiparallel ß­strands with 4-6 surrounding alpha­helices. The manganese atom is liganded by two residues from each of N­terminal helices and two residues from the loops in the C­terminal domain.

The active site manganese is pentacoordinate, with the metal ligands (Nepsilon of three conserved His residues, Odelta of the conserved Asp residue and a water molecule) arranged in distorted trigonal bipyramidal geometry. The first His residue and a solvent molecule fill the two axial positions. In the azide-MnIII-SOD complex, the manganese becomes hexacoordinate with distorted octahedral geometry, with azide coordinated trans to Asp ligand [7]. The table below lists the mononuclear manganese environment residues in known 3­D structures.

Enzyme Quaternary
structure		 Mononuclear iron environment residues PDB code Ref.
Escherichia coli Mn-SOD dimer
His­26
His­81
Asp­167
His­171
1vew
[6]
Human mitochondrial Mn-SOD tetramer
His­26
His­74
Asp­159
His­163
1abm
[7]
Propionibacterium freudenreichii cambialistic SOD tetramer
His­27
His­75
Asp­161
His­165
1ar4
[8]
Thermus thermophilus Mn-SOD tetramer
His­28
His­83
Asp­166
His­170
1mng
[9]

Thermodynamic properties of Mn-SOD

Protein ProTherm
entry		 Mutation Method
Manganese superoxide dismutase (pH 7.8); human mitochondrial 3098 wild type thermal
3099 I58T thermal

Mn-SOD in enzyme databases

ENZYME LIGAND BRENDA Official name Alternative names
1.15.1.1 1.15.11.1 1.15.1.1 Superoxide dismutase Ferrisuperoxide dismutase; Fe-SOD

Mn-SOD in motif databases

PRINTS ID PRINTS AC PROSITE/BLOCKS ID PROSITE AC BLOCKS AC
-
-
 SOD_MN PS00088 BL00088

Mn-SOD in alignment databases

Protein Superfamily Pfam LPFC 3­D alignment
00206; superoxide dismutase (Fe/Mn)
PF00081; sodfe
-

Mn-SOD in 3­D databases

Mn-superoxide dismutase contain a single manganese atom per monomer.

PDB MSD scop BSMRELI
Base		 Header MMS Abstract ¹
1abm 1abm 1abm 1abm 1abm Mn(II)-superoxide dismutase; human mitochondrial
-
1ap5 1ap5 1ap5 1ap5 1ap5 Mn(II)-superoxide dismutase (Y34F mutant); human mitochondrial
-
1ap6 1ap6 1ap6 1ap6 1ap6 Mn(II)-superoxide dismutase (Y34F mutant); human mitochondrial
-
1ar4 1ar4 1ar4 1ar4 1ar4 Cambialistic superoxide dismutase [Mn bound]; Propionibacterium freudenreichii subspec. Shermanii
-
1mng 1mng 1mng 1mng 1mng Mn(III)-superoxide dismutase (complex with azide); Thermus thermophilus strain HB8
-
1msd 1msd 1msd 1msd 1msd Mn(III)-superoxide dismutase; human mitochondrial
-
1qnm 1qnm 1qnm 1qnm 1qnm Mn(II)-superoxide dismutase (Q143N mutant); human mitochondrial
-
1var 1var 1var 1var 1var Mn(III)-superoxide dismutase (I58T mutant); human mitochondrial
-
1vew 1vew 1vew 1vew 1vew Mn(II)-superoxide dismutase (complex with OH¯); Escherichia coli
-
3mds 3mds 3mds 3mds 3mds Mn(II)-superoxide dismutase; Thermus thermophilus strain HB8
-

¹ Macromolecular Structures abstract. Full text is available to BioMedNet Members

References

  1. Parker, M.W., Blake, C.C., Barra, D., Bossa, F., Schinina, M.E., Bannister, W.H. and Bannister, J.V. (1987) Structural identity between the iron­ and manganese­containing superoxide dismutases. Protein Engineering 1, 393-397.
  2. Parker, M.W. and Blake, C.C. (1988) Iron­ and manganese­containing superoxide dismutases can be distinguished by analysis of their primary structures. FEBS Lett. 229, 377-382.
  3. Grace, S.C. (1990) Phylogenetic distribution of superoxide dismutase supports an endosymbiotic origin for chloroplasts and mitochondria. Life Sci. 47, 1875-1886.
  4. Beyer, W.F., Jr., Reynolds, J.A. and Fridovich, I. (1989) Differences between the manganese­ and the iron­containing superoxide dismutases of Escherichia coli detected through sedimentation equilibrium, hydrodynamic, and spectroscopic studies. Biochemistry 28, 4403-4409.
  5. Sehn, A.P. and Meier, B. (1994) Regulation of an in vivo metal­exchangeable superoxide dismutase from Propionibacterium shermanii exhibiting activity with different metal cofactors. Biochem. J. 304, 803-808.
  6. Edwards, R.A., Baker, H.M., Whittaker, M.M., Whittaker, J.W., Jameson, G.B. and Baker, E.N. (1998) Crystal structure of Escherichia coli manganese superoxide dismutase at 2.1­Å resolution. J. Biol. Inorg. Chem. 3, 161-171.
  7. Borgstahl, G.E.O., Parge, H.E., Hickey, M.J., Beyer, W.F., Jr., Hallewell, R.A. and Tainer, J.A. (1992) The structure of human mitochondrial manganese superoxide dismutase reveals a novel tetrameric interface of two 4­helix bundles. Cell 71, 107-118.
  8. Schmidt, M., Meier, B. and Parak, F. (1996) X­ray structure of the cambialistic superoxide dismutase from Propionibacterium shermanii active with Fe or Mn. J. Biol. Inorg. Chem. 1, 532-541.
  9. Lah, M.S., Dixon, M.M., Pattridge, K.A., Stallings, W.C., Fee, J.A. and Ludwig, M.L. (1995) Structure-function in Escherichia coli iron superoxide dismutase: Comparisons with the manganese enzyme from Thermus thermophilus. Biochemistry 34, 1646-1660.
Bibliography on structural studies of Mn-superoxide dismutase
Reviews on superoxide dismutases