1. Subunit asymmetry in the three-dimensional structure of a human CuZnSOD mutant found in familial amyotrophic lateral sclerosis
- Author
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Joan Selverstone Valentine, Edith Butler Gralla, Aram M. Nersissian, David Eisenberg, H. Liu, Matteo Pellegrini, and P.J. Hart
- Subjects
Models, Molecular ,Protein Conformation ,Protein subunit ,Mutant ,Glycine ,chemistry.chemical_element ,Crystal structure ,Saccharomyces cerevisiae ,Arginine ,Crystallography, X-Ray ,Ligands ,Biochemistry ,Superoxide dismutase ,Structure-Activity Relationship ,Protein structure ,Humans ,Point Mutation ,Binding site ,Molecular Biology ,Binding Sites ,biology ,Ligand ,Superoxide Dismutase ,Amyotrophic Lateral Sclerosis ,Copper ,Recombinant Proteins ,Crystallography ,Zinc ,chemistry ,biology.protein ,Biophysics ,Dimerization ,Research Article - 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 angstroms 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 angstroms2) than subunit(broken) ((B) = 24 +/- 11 angstroms2). 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.
- Published
- 1998