1SPD

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

1SPD の概要

• エントリーDOI: 10.2210/pdb1spd/pdb
• 分子名称: SUPEROXIDE DISMUTASE, COPPER (II) ION, ZINC ION (3 entities in total)
• 機能のキーワード: oxidoreductase, superoxide acceptor
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 31965.11

構造登録者

Parge, H.E.,Tainer, J.A. (登録日: 1993-07-21, 公開日: 1994-04-30, 最終更新日: 2024-10-30)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.4 Å)