2WKO

Structure of metal loaded Pathogenic SOD1 Mutant G93A.

Summary for 2WKO

• Entry DOI: 10.2210/pdb2wko/pdb
• Related: 1AZV 1BA9 1DSW 1FUN 1HL4 1HL5 1KMG 1L3N 1MFM 1N18 1N19 1OEZ 1OZT 1OZU 1P1V 1PTZ 1PU0 1RK7 1SOS 1SPD 1UXL 1UXM 2AF2 2C9S 2C9U 2C9V 2V0A 2VR6 2VR7 2VR8 3GZO 3GZP 3GZQ 4SOD
• Descriptor: SUPEROXIDE DISMUTASE [CU-ZN], COPPER (II) ION, ZINC ION, ... (6 entities in total)
• Functional Keywords: amyotrophic lateral sclerosis, phosphoprotein, oxidoreductase, disease mutation, neurodegeneration, acetylation, antioxidant, metal-binding
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Cytoplasm: P00441 P00441
• Total number of polymer chains: 2
• Total formula weight: 32389.87

Authors

Antonyuk, S.V.,Galaleldeen, A.,Strange, R.,Whitson, L.,Narayana, N.,Taylor, A.,Schuermann, J.P.,Holloway, S.P.,Hasnain, S.S.,Hart, P.J. (deposition date: 2009-06-16, release date: 2009-11-24, Last modification date: 2023-12-13)

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-, 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 (1.97 Å)