4A7T

Structure of human I113T SOD1 mutant complexed with isoproteranol in the p21 space group

4A7T の概要

• エントリーDOI: 10.2210/pdb4a7t/pdb
• 関連するPDBエントリー: 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 2WKO 2WYT 2WYZ 2WZ0 2WZ5 2WZ6 2XJK 2XJL 4A7G 4A7Q 4A7R 4A7S 4A7U 4A7V 4SOD
• 分子名称: SUPEROXIDE DISMUTASE [CU-ZN], ISOPRENALINE, SULFATE ION, ... (7 entities in total)
• 機能のキーワード: oxidoreductase, amyotrophic lateral sclerosis, antioxidant, disease mutation, metal-binding, zn superoxide dismutase
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Cytoplasm: P00441
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 33447.56

構造登録者

Wright, G.S.A.,Kershaw, N.M.,Antonyuk, S.V.,Strange, R.W.,ONeil, P.M.,Hasnain, S.S. (登録日: 2011-11-14, 公開日: 2012-11-28, 最終更新日: 2024-11-06)

主引用文献

Wright, G.S.A.,Antonyuk, S.V.,Kershaw, N.M.,Strange, R.W.,Hasnain, S.S.
Ligand Binding and Aggregation of Pathogenic Sod1.
Nat.Commun., 4:1758-, 2013

PubMed Abstract: Mutations in the gene encoding Cu/Zn superoxide dismutase-1 cause amyotrophic lateral sclerosis. Superoxide dismutase-1 mutations decrease protein stability and promote aggregation. The mutant monomer is thought to be an intermediate in the pathway from the superoxide dismutase-1 dimer to aggregate. Here we find that the monomeric copper-apo, zinc-holo protein is structurally perturbed and the apo-protein aggregates without reattainment of the monomer-dimer equilibrium. Intervention to stabilize the superoxide dismutase-1 dimer and inhibit aggregation is regarded as a potential therapeutic strategy. We describe protein-ligand interactions for two compounds, Isoproterenol and 5-fluorouridine, highlighted as superoxide dismutase-1 stabilizers. We find both compounds interact with superoxide dismutase-1 at a key region identified at the core of the superoxide dismutase-1 fibrillar aggregates, β-barrel loop II-strand 3, rather than the proposed dimer interface site. This illustrates the need for direct structural observations when developing compounds for protein-targeted therapeutics.

PubMed: 23612299
DOI: 10.1038/NCOMMS2750

実験手法

X-RAY DIFFRACTION (1.45 Å)