5OD2

Crystal structure of ADP-dependent glucokinase from Methanocaldococcus jannaschii

5OD2 の概要

• エントリーDOI: 10.2210/pdb5od2/pdb
• 分子名称: Bifunctional ADP-specific glucokinase/phosphofructokinase, alpha-D-glucopyranose, (2R,3R,4S,5R)-2-(4-AMINO-5-IODO-7H-PYRROLO[2,3-D]PYRIMIDIN-7-YL)-5-(HYDROXYMETHYL)TETRAHYDROFURAN-3,4-DIOL, ... (6 entities in total)
• 機能のキーワード: sugar metabolism, protein-inhibitor complex, transferase
• 由来する生物種: Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440)
• 細胞内の位置: Cytoplasm: Q58999
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 161089.93

構造登録者

Wisniewska, M.,Tokarz, P.,Grudnik, P. (登録日: 2017-07-04, 公開日: 2018-01-31, 最終更新日: 2024-01-17)

主引用文献

Tokarz, P.,Wisniewska, M.,Kaminski, M.M.,Dubin, G.,Grudnik, P.
Crystal structure of ADP-dependent glucokinase from Methanocaldococcus jannaschii in complex with 5-iodotubercidin reveals phosphoryl transfer mechanism.
Protein Sci., 27:790-797, 2018

PubMed Abstract: ADP-dependent glucokinase (ADPGK) is an alternative novel glucose phosphorylating enzyme in a modified glycolysis pathway of hyperthermophilic Archaea. In contrast to classical ATP-dependent hexokinases, ADPGK utilizes ADP as a phosphoryl group donor. Here, we present a crystal structure of archaeal ADPGK from Methanocaldococcus jannaschii in complex with an inhibitor, 5-iodotubercidin, d-glucose, inorganic phosphate, and a magnesium ion. Detailed analysis of the architecture of the active site allowed for confirmation of the previously proposed phosphorylation mechanism and the crucial role of the invariant arginine residue (Arg197). The crystal structure shows how the phosphate ion, while mimicking a β-phosphate group, is positioned in the proximity of the glucose moiety by arginine and the magnesium ion, thus providing novel insights into the mechanism of catalysis. In addition, we demonstrate that 5-iodotubercidin inhibits human ADPGK-dependent T cell activation-induced reactive oxygen species (ROS) release and downstream gene expression, and as such it may serve as a model compound for further screening for hADPGK-specific inhibitors.

PubMed: 29352744
DOI: 10.1002/pro.3377

実験手法

X-RAY DIFFRACTION (1.98 Å)