title: Subunit asymmetry in the three-dimensional structure of a human CuZnSOD mutant found in familial amyotrophic lateral sclerosis.
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.
authors.affiliation: UCLA-DOE Laboratory of Structural Biology and Molecular Medicine, University of California, Los Angeles 90095, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Hart
authors.forename: H
authors.initials: H
authors.lastname: Liu
authors.forename: M
authors.initials: M
authors.lastname: Pellegrini
authors.forename: A M
authors.initials: AM
authors.lastname: Nersissian
authors.forename: E B
authors.initials: EB
authors.lastname: Gralla
authors.forename: J S
authors.initials: JS
authors.lastname: Valentine
authors.forename: D
authors.initials: D
authors.lastname: Eisenberg
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology*; D001120:Arginine; D001665:Binding Sites; D003300:Copper; D018360:Crystallography, X-Ray; D019281:Dimerization; D005998:Glycine; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D017354:Point Mutation; D011487:Protein Conformation; D011994:Recombinant Proteins; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013329:Structure-Activity Relationship; D013482:Superoxide Dismutase / Q000235:genetics; D015032:Zinc
chemical_list: D008024:Ligands; D011994:Recombinant Proteins; D003300:Copper; D001120:Arginine; D013482:Superoxide Dismutase; D015032:Zinc; D005998:Glycine