3GZQ

HUMAN SOD1 A4V Metal-free Variant

Summary for 3GZQ

• Entry DOI: 10.2210/pdb3gzq/pdb
• Related: 3GZO 3GZP
• Descriptor: Superoxide dismutase [Cu-Zn], SULFATE ION (3 entities in total)
• Functional Keywords: oxidoreductase, human cu, zn superoxide dismutase, antioxidant, metal-binding, copper, zinc, amyotrophic lateral sclerosis, disease mutation, acetylation, cytoplasm, apo, disulfide bond, phosphoprotein, ubl conjugation
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm: P00441
• Total number of polymer chains: 2
• Total formula weight: 31955.43

Authors

Galaleldeen, A.,Taylor, A.B.,Whitson, L.J.,Hart, P.J. (deposition date: 2009-04-07, release date: 2009-10-13, Last modification date: 2024-11-20)

Primary citation

Galaleldeen, A.,Strange, R.W.,Whitson, L.J.,Antonyuk, S.V.,Narayana, N.,Taylor, A.B.,Schuermann, J.P.,Holloway, S.P.,Hasnain, S.S.,Hart, P.J.
Structural and biophysical properties of metal-free pathogenic SOD1 mutants A4V and G93A.
Arch.Biochem.Biophys., 492:40-47, 2009

PubMed Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurodegenerative disease characterized by the destruction of motor neurons in the spinal cord and brain. A subset of ALS cases are linked to dominant mutations in copper-zinc superoxide dismutase (SOD1). The pathogenic SOD1 variants A4V and G93A have been the foci of multiple studies aimed at understanding the molecular basis for SOD1-linked ALS. The A4V variant is responsible for the majority of familial ALS cases in North America, causing rapidly progressing paralysis once symptoms begin and the G93A SOD1 variant is overexpressed in often studied murine models of the disease. Here we report the three-dimensional structures of metal-free A4V and of metal-bound and metal-free G93A SOD1. In the metal-free structures, the metal-binding loop elements are observed to be severely disordered, suggesting that these variants may share mechanisms of aggregation proposed previously for other pathogenic SOD1 proteins.

PubMed: 19800308
DOI: 10.1016/j.abb.2009.09.020

Experimental method

X-RAY DIFFRACTION (1.401 Å)