3CQQ

Human SOD1 G85R Variant, Structure II

3CQQ の概要

• エントリーDOI: 10.2210/pdb3cqq/pdb
• 関連するPDBエントリー: 3CQP
• 分子名称: Superoxide dismutase [Cu-Zn], ZINC ION, ACETYL GROUP, ... (4 entities in total)
• 機能のキーワード: oxidoreductase, human cu, zn superoxide dismutase, antioxidant, metal-binding, amyotrophic lateral sclerosis, disease mutation
• 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: 32127.69

構造登録者

Cao, X.,Antonyuk, S.,Whitson, L.J.,Taylor, A.B.,Holloway, S.P.,Strange, R.W.,Doucette, P.A.,Valentine, J.S.,Tiwari, A.,Hayward, L.J.,Padua, S.,Cohlberg, J.A.,Hasnain, S.S.,Hart, P.J. (登録日: 2008-04-03, 公開日: 2008-04-29, 最終更新日: 2023-08-30)

主引用文献

Cao, X.,Antonyuk, S.V.,Seetharaman, S.V.,Whitson, L.J.,Taylor, A.B.,Holloway, S.P.,Strange, R.W.,Doucette, P.A.,Valentine, J.S.,Tiwari, A.,Hayward, L.J.,Padua, S.,Cohlberg, J.A.,Hasnain, S.S.,Hart, P.J.
Structures of the G85R Variant of SOD1 in Familial Amyotrophic Lateral Sclerosis.
J.Biol.Chem., 283:16169-16177, 2008

PubMed Abstract: Mutations in the gene encoding human copper-zinc superoxide dismutase (SOD1) cause a dominant form of the progressive neurodegenerative disease amyotrophic lateral sclerosis. Transgenic mice expressing the human G85R SOD1 variant develop paralytic symptoms concomitant with the appearance of SOD1-enriched proteinaceous inclusions in their neural tissues. The process(es) through which misfolding or aggregation of G85R SOD1 induces motor neuron toxicity is not understood. Here we present structures of the human G85R SOD1 variant determined by single crystal x-ray diffraction. Alterations in structure of the metal-binding loop elements relative to the wild type enzyme suggest a molecular basis for the metal ion deficiency of the G85R SOD1 protein observed in the central nervous system of transgenic mice and in purified recombinant G85R SOD1. These findings support the notion that metal-deficient and/or disulfide-reduced mutant SOD1 species contribute to toxicity in SOD1-linked amyotrophic lateral sclerosis.

PubMed: 18378676
DOI: 10.1074/jbc.M801522200

実験手法

X-RAY DIFFRACTION (1.9 Å)