Subunit asymmetry in the three-dimensional structure of a human CuZnSOD mutant found in familial amyotrophic lateral sclerosis

P. John Hart, Hongbin Liu, Matteo Pellegrini, Aram M. Nersissian, Edith B. Gralla, Joan S. Valentine, David Eisenberg

Research output: Contribution to journalArticle

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Abstract

The X-ray crystal structure of a human copper/zinc superoxide dismutase mutant (G37R CuZnSOD) found in some patients with the inherited form of Lou Gehrig's disease (FALS) has been determined to 1.9 Å resolution. The two SOD subunits have distinct environments in the crystal and are different in structure at their copper binding sites. One subunit (subunit(intact)) shows a four-coordinate ligand geometry of the copper ion, whereas the other subunit (subunit(broken)) shows a three-coordinate geometry of the copper ion. Also, subunit(intact) displays higher atomic displacement parameters for backbone atoms (<B> = 30 ± 10 Å2) than subunit(broken) (<B> = 24 ± 11 Å2). This structure is the first CuZnSOD to show large differences between the two subunits. Factors that may contribute to these differences are discussed and a possible link of a looser structure to FALS is suggested.

Original languageEnglish (US)
Pages (from-to)545-555
Number of pages11
JournalProtein Science
Volume7
Issue number3
StatePublished - Mar 1998
Externally publishedYes

Fingerprint

Copper
Ions
Geometry
Amyotrophic Lateral Sclerosis
Superoxide Dismutase
Zinc
Crystal structure
Display devices
Binding Sites
X-Rays
Ligands
X rays
Atoms
Crystals
Amyotrophic lateral sclerosis 1

Keywords

  • Amyotrophic lateral sclerosis
  • Apoptosis
  • Lou Gehrig's disease
  • Motor neuron
  • Neurodegeneration
  • Oxidative damage
  • Superoxide dismutase
  • X-ray crystallography

ASJC Scopus subject areas

  • Biochemistry

Cite this

Hart, P. J., Liu, H., Pellegrini, M., Nersissian, A. M., Gralla, E. B., Valentine, J. S., & Eisenberg, D. (1998). Subunit asymmetry in the three-dimensional structure of a human CuZnSOD mutant found in familial amyotrophic lateral sclerosis. Protein Science, 7(3), 545-555.

Subunit asymmetry in the three-dimensional structure of a human CuZnSOD mutant found in familial amyotrophic lateral sclerosis. / Hart, P. John; Liu, Hongbin; Pellegrini, Matteo; Nersissian, Aram M.; Gralla, Edith B.; Valentine, Joan S.; Eisenberg, David.

In: Protein Science, Vol. 7, No. 3, 03.1998, p. 545-555.

Research output: Contribution to journalArticle

Hart, PJ, Liu, H, Pellegrini, M, Nersissian, AM, Gralla, EB, Valentine, JS & Eisenberg, D 1998, 'Subunit asymmetry in the three-dimensional structure of a human CuZnSOD mutant found in familial amyotrophic lateral sclerosis', Protein Science, vol. 7, no. 3, pp. 545-555.
Hart, P. John ; Liu, Hongbin ; Pellegrini, Matteo ; Nersissian, Aram M. ; Gralla, Edith B. ; Valentine, Joan S. ; Eisenberg, David. / Subunit asymmetry in the three-dimensional structure of a human CuZnSOD mutant found in familial amyotrophic lateral sclerosis. In: Protein Science. 1998 ; Vol. 7, No. 3. pp. 545-555.
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