4QKB

Crystal structure of seleno-methionine labelled human ALKBH7 in complex with alpha-ketoglutarate and Mn(II)

4QKB の概要

• エントリーDOI: 10.2210/pdb4qkb/pdb
• 関連するPDBエントリー: 4NRO 4O7X 4QKD 4QKF
• 分子名称: Alpha-ketoglutarate-dependent dioxygenase alkB homolog 7, mitochondrial, MANGANESE (II) ION, 2-OXOGLUTARIC ACID, ... (4 entities in total)
• 機能のキーワード: alkbh7, dioxygenase, metal-binding, oxidoreductase, programmed necrosis, fat metabolism
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Mitochondrion matrix : Q9BT30
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 69235.23

構造登録者

Wang, G.,He, Q.,Chen, Z. (登録日: 2014-06-05, 公開日: 2014-08-20, 最終更新日: 2024-10-30)

主引用文献

Wang, G.,He, Q.,Feng, C.,Liu, Y.,Deng, Z.,Qi, X.,Wu, W.,Mei, P.,Chen, Z.
The atomic resolution structure of human AlkB homolog 7 (ALKBH7), a key protein for programmed necrosis and fat metabolism
J.Biol.Chem., 289:27924-27936, 2014

PubMed Abstract: ALKBH7 is the mitochondrial AlkB family member that is required for alkylation- and oxidation-induced programmed necrosis. In contrast to the protective role of other AlkB family members after suffering alkylation-induced DNA damage, ALKBH7 triggers the collapse of mitochondrial membrane potential and promotes cell death. Moreover, genetic ablation of mouse Alkbh7 dramatically increases body weight and fat mass. Here, we present crystal structures of human ALKBH7 in complex with Mn(II) and α-ketoglutarate at 1.35 Å or N-oxalylglycine at 2.0 Å resolution. ALKBH7 possesses the conserved double-stranded β-helix fold that coordinates a catalytically active iron by a conserved HX(D/E) … Xn … H motif. Self-hydroxylation of Leu-110 was observed, indicating that ALKBH7 has the potential to catalyze hydroxylation of its substrate. Unlike other AlkB family members whose substrates are DNA or RNA, ALKBH7 is devoid of the "nucleotide recognition lid" which is essential for binding nucleobases, and thus exhibits a solvent-exposed active site; two loops between β-strands β6 and β7 and between β9 and β10 create a special outer wall of the minor β-sheet of the double-stranded β-helix and form a negatively charged groove. These distinct features suggest that ALKBH7 may act on protein substrate rather than nucleic acids. Taken together, our findings provide a structural basis for understanding the distinct function of ALKBH7 in the AlkB family and offer a foundation for drug design in treating cell death-related diseases and metabolic diseases.

PubMed: 25122757
DOI: 10.1074/jbc.M114.590505

実験手法

X-RAY DIFFRACTION (2.6 Å)