2W8Q

The crystal structure of human SSADH in complex with SSA.

2W8Q の概要

• エントリーDOI: 10.2210/pdb2w8q/pdb
• 関連するPDBエントリー: 2W8N 2W8O 2W8P 2W8R
• 分子名称: SUCCINATE-SEMIALDEHYDE DEHYDROGENASE, MITOCHONDRIAL, SULFATE ION, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: mitochondrion, dehydrogenase, oxidoreductase, transit peptide, disease mutation, ssa, nad, ssadh, polymorphism, mitochondria
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Mitochondrion: P51649
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 53425.43

構造登録者

Kim, Y.-G.,Kim, K.-J. (登録日: 2009-01-19, 公開日: 2009-06-09, 最終更新日: 2024-05-08)

主引用文献

Kim, Y.-G.,Lee, S.,Kwon, O.-S.,Park, S.-Y.,Lee, S.-J.,Park, B.-J.,Kim, K.-J.
Redox-Switch Modulation of Human Ssadh by Dynamic Catalytic Loop.
Embo J., 28:959-, 2009

PubMed Abstract: Succinic semialdehyde dehydrogenase (SSADH) is involved in the final degradation step of the inhibitory neurotransmitter gamma-aminobutyric acid by converting succinic semialdehyde to succinic acid in the mitochondrial matrix. SSADH deficiency, a rare autosomal recessive disease, exhibits variable clinical phenotypes, including psychomotor retardation, language delay, behaviour disturbance and convulsions. Here, we present crystal structures of both the oxidized and reduced forms of human SSADH. Interestingly, the structures show that the catalytic loop of the enzyme undergoes large structural changes depending on the redox status of the environment, which is mediated by a reversible disulphide bond formation between a catalytic Cys340 and an adjacent Cys342 residues located on the loop. Subsequent in vivo and in vitro studies reveal that the 'dynamic catalytic loop' confers a response to reactive oxygen species and changes in redox status, indicating that the redox-switch modulation could be a physiological control mechanism of human SSADH. Structural basis for the substrate specificity of the enzyme and the impact of known missense point mutations associated with the disease pathogenesis are presented as well.

PubMed: 19300440
DOI: 10.1038/EMBOJ.2009.40

実験手法

X-RAY DIFFRACTION (2.4 Å)