Skip to main content
PMC home page
Protein Science : A Publication of the Protein Society logoLink to Protein Science : A Publication of the Protein Society
. 1993 May;2(5):814–825. doi: 10.1002/pro.5560020511

Comparison of the crystal structures of genetically engineered human manganese superoxide dismutase and manganese superoxide dismutase from Thermus thermophilus: differences in dimer-dimer interaction.

U G Wagner 1, K A Pattridge 1, M L Ludwig 1, W C Stallings 1, M M Werber 1, C Oefner 1, F Frolow 1, J L Sussman 1
PMCID: PMC2142493  PMID: 8495200

Abstract

The three-dimensional X-ray structure of a recombinant human mitochondrial manganese superoxide dismutase (MnSOD) (chain length 198 residues) was determined by the method of molecular replacement using the related structure of MnSOD from Thermus thermophilus as a search model. This tetrameric human MnSOD crystallizes in space group P2(1)2(1)2 with a dimer in the asymmetric unit (Wagner, U.G., Werber, M.M., Beck, Y., Hartman, J.R., Frolow, F., & Sussman, J.L., 1989, J. Mol. Biol. 206, 787-788). Refinement of the protein structure (3,148 atoms with Mn and no solvents), with restraints maintaining noncrystallographic symmetry, converged at an R-factor of 0.207 using all data from 8.0 to 3.2 A resolution and group thermal parameters. The monomer-monomer interactions typical of bacterial Fe- and Mn-containing SODs are retained in the human enzyme, but the dimer-dimer interactions that form the tetramer are very different from those found in the structure of MnSOD from T. thermophilus. In human MnSOD one of the dimers is rotated by 84 degrees relative to its equivalent in the thermophile enzyme. As a result the monomers are arranged in an approximately tetrahedral array, the dimer-dimer packing is more intimate than observed in the bacterial MnSOD from T. thermophilus, and the dimers interdigitate. The metal-ligand interactions, determined by refinement and verified by computation of omit maps, are identical to those observed in T. thermophilus MnSOD.

Full Text

The Full Text of this article is available as a PDF (5.2 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bannister J. V., Bannister W. H., Rotilio G. Aspects of the structure, function, and applications of superoxide dismutase. CRC Crit Rev Biochem. 1987;22(2):111–180. doi: 10.3109/10409238709083738. [DOI] [PubMed] [Google Scholar]
  2. Barra D., Schinina M. E., Simmaco M., Bannister J. V., Bannister W. H., Rotilio G., Bossa F. The primary structure of human liver manganese superoxide dismutase. J Biol Chem. 1984 Oct 25;259(20):12595–12601. [PubMed] [Google Scholar]
  3. Beck Y., Oren R., Amit B., Levanon A., Gorecki M., Hartman J. R. Human Mn superoxide dismutase cDNA sequence. Nucleic Acids Res. 1987 Nov 11;15(21):9076–9076. doi: 10.1093/nar/15.21.9076. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Borgstahl G. E., Parge H. E., Hickey M. J., Beyer W. F., Jr, Hallewell R. A., Tainer J. A. The structure of human mitochondrial manganese superoxide dismutase reveals a novel tetrameric interface of two 4-helix bundles. Cell. 1992 Oct 2;71(1):107–118. doi: 10.1016/0092-8674(92)90270-m. [DOI] [PubMed] [Google Scholar]
  5. Bridgen J., Harris J. I., Kolb E. Superoxide dismutase from Bacillus stearothermophilus: crystallization and preliminary x-ray diffraction studies. J Mol Biol. 1976 Aug 5;105(2):333–335. doi: 10.1016/0022-2836(76)90116-9. [DOI] [PubMed] [Google Scholar]
  6. Carlioz A., Ludwig M. L., Stallings W. C., Fee J. A., Steinman H. M., Touati D. Iron superoxide dismutase. Nucleotide sequence of the gene from Escherichia coli K12 and correlations with crystal structures. J Biol Chem. 1988 Jan 25;263(3):1555–1562. [PubMed] [Google Scholar]
  7. Deutsch H. F., Hoshi S., Matsuda Y., Suzuki K., Kawano K., Kitagawa Y., Katsube Y., Taniguchi N. Preparation of human manganese superoxide dismutase by tri-phase partitioning and preliminary crystallographic data. J Mol Biol. 1991 May 5;219(1):103–108. doi: 10.1016/0022-2836(91)90860-9. [DOI] [PubMed] [Google Scholar]
  8. Gorecki M., Beck Y., Hartman J. R., Fischer M., Weiss L., Tochner Z., Slavin S., Nimrod A. Recombinant human superoxide dismutases: production and potential therapeutical uses. Free Radic Res Commun. 1991;12-13 Pt 1:401–410. doi: 10.3109/10715769109145810. [DOI] [PubMed] [Google Scholar]
  9. Hope H. Cryocrystallography of biological macromolecules: a generally applicable method. Acta Crystallogr B. 1988 Feb 1;44(Pt 1):22–26. doi: 10.1107/s0108768187008632. [DOI] [PubMed] [Google Scholar]
  10. Kabsch W., Sander C. Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers. 1983 Dec;22(12):2577–2637. doi: 10.1002/bip.360221211. [DOI] [PubMed] [Google Scholar]
  11. Klug-Roth D., Fridovich I., Rabani J. Pulse radiolytic investigations of superoxide catalyzed disproportionation. Mechanism for bovine superoxide dismutase. J Am Chem Soc. 1973 May 2;95(9):2786–2790. doi: 10.1021/ja00790a007. [DOI] [PubMed] [Google Scholar]
  12. McAdam M. E., Fox R. A., Lavelle F., Fielden E. M. A pulse-radiolysis study of the manganese-containing superoxide dismutase from Bacillus stearothermophilus. A kinetic model for the enzyme action. Biochem J. 1977 Jul 1;165(1):71–79. doi: 10.1042/bj1650071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. McCord J. M. Free radicals and myocardial ischemia: overview and outlook. Free Radic Biol Med. 1988;4(1):9–14. doi: 10.1016/0891-5849(88)90005-6. [DOI] [PubMed] [Google Scholar]
  14. Miller S. The structure of interfaces between subunits of dimeric and tetrameric proteins. Protein Eng. 1989 Nov;3(2):77–83. doi: 10.1093/protein/3.2.77. [DOI] [PubMed] [Google Scholar]
  15. Parizada B., Werber M. M., Nimrod A. Protective effects of human recombinant MnSOD in adjuvant arthritis and bleomycin-induced lung fibrosis. Free Radic Res Commun. 1991;15(5):297–301. doi: 10.3109/10715769109105225. [DOI] [PubMed] [Google Scholar]
  16. Parker M. W., Blake C. C. Crystal structure of manganese superoxide dismutase from Bacillus stearothermophilus at 2.4 A resolution. J Mol Biol. 1988 Feb 20;199(4):649–661. doi: 10.1016/0022-2836(88)90308-7. [DOI] [PubMed] [Google Scholar]
  17. Ringe D., Petsko G. A., Yamakura F., Suzuki K., Ohmori D. Structure of iron superoxide dismutase from Pseudomonas ovalis at 2.9-A resolution. Proc Natl Acad Sci U S A. 1983 Jul;80(13):3879–3883. doi: 10.1073/pnas.80.13.3879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Stallings W. C., Metzger A. L., Pattridge K. A., Fee J. A., Ludwig M. L. Structure-function relationships in iron and manganese superoxide dismutases. Free Radic Res Commun. 1991;12-13 Pt 1:259–268. doi: 10.3109/10715769109145794. [DOI] [PubMed] [Google Scholar]
  19. Stallings W. C., Pattridge K. A., Strong R. K., Ludwig M. L. Manganese and iron superoxide dismutases are structural homologs. J Biol Chem. 1984 Sep 10;259(17):10695–10699. [PubMed] [Google Scholar]
  20. Stallings W. C., Pattridge K. A., Strong R. K., Ludwig M. L. The structure of manganese superoxide dismutase from Thermus thermophilus HB8 at 2.4-A resolution. J Biol Chem. 1985 Dec 25;260(30):16424–16432. [PubMed] [Google Scholar]
  21. Stoddard B. L., Howell P. L., Ringe D., Petsko G. A. The 2.1-A resolution structure of iron superoxide dismutase from Pseudomonas ovalis. Biochemistry. 1990 Sep 25;29(38):8885–8893. doi: 10.1021/bi00490a002. [DOI] [PubMed] [Google Scholar]
  22. Tainer J. A., Getzoff E. D., Beem K. M., Richardson J. S., Richardson D. C. Determination and analysis of the 2 A-structure of copper, zinc superoxide dismutase. J Mol Biol. 1982 Sep 15;160(2):181–217. doi: 10.1016/0022-2836(82)90174-7. [DOI] [PubMed] [Google Scholar]
  23. Ward K. B., Wishner B. C., Lattman E. E., Love W. E. Structure of deoxyhemoglobin A crystals grown from polyethylene glycol solutions. J Mol Biol. 1975 Oct 15;98(1):161–177. doi: 10.1016/s0022-2836(75)80107-0. [DOI] [PubMed] [Google Scholar]
  24. Werber M. M., Greenstein L. A. Biochemical and stability properties of recombinant human MnSOD. Free Radic Res Commun. 1991;12-13 Pt 1:335–348. doi: 10.3109/10715769109145803. [DOI] [PubMed] [Google Scholar]

Articles from Protein Science : A Publication of the Protein Society are provided here courtesy of The Protein Society

RESOURCES