1SPD

AMYOTROPHIC LATERAL SCLEROSIS AND STRUCTURAL DEFECTS IN CU,ZN SUPEROXIDE DISMUTASE

Summary for 1SPD

• Entry DOI: 10.2210/pdb1spd/pdb
• Descriptor: SUPEROXIDE DISMUTASE, COPPER (II) ION, ZINC ION (3 entities in total)
• Functional Keywords: oxidoreductase, superoxide acceptor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 31965.11

Authors

Parge, H.E.,Tainer, J.A. (deposition date: 1993-07-21, release date: 1994-04-30, Last modification date: 2024-10-30)

Primary citation

Deng, H.X.,Hentati, A.,Tainer, J.A.,Iqbal, Z.,Cayabyab, A.,Hung, W.Y.,Getzoff, E.D.,Hu, P.,Herzfeldt, B.,Roos, R.P.,Warner, C.,Deng, G.,Soriano, E.,Smyth, C.,Parge, H.E.,Ahmed, A.,Roses, A.D.,Hallewell, R.A.,Pericak-Vance, M.A.,Siddique, T.
Amyotrophic lateral sclerosis and structural defects in Cu,Zn superoxide dismutase.
Science, 261:1047-1051, 1993

PubMed Abstract: Single-site mutants in the Cu,Zn superoxide dismutase (SOD) gene (SOD1) occur in patients with the fatal neurodegenerative disorder familial amyotrophic lateral sclerosis (FALS). Complete screening of the SOD1 coding region revealed that the mutation Ala4 to Val in exon 1 was the most frequent one; mutations were identified in exons 2, 4, and 5 but not in the active site region formed by exon 3. The 2.4 A crystal structure of human SOD, along with two other SOD structures, established that all 12 observed FALS mutant sites alter conserved interactions critical to the beta-barrel fold and dimer contact, rather than catalysis. Red cells from heterozygotes had less than 50 percent normal SOD activity, consistent with a structurally defective SOD dimer. Thus, defective SOD is linked to motor neuron death and carries implications for understanding and possible treatment of FALS.

PubMed: 8351519

Experimental method

X-RAY DIFFRACTION (2.4 Å)