5OD2

Crystal structure of ADP-dependent glucokinase from Methanocaldococcus jannaschii

Summary for 5OD2

• Entry DOI: 10.2210/pdb5od2/pdb
• Descriptor: 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)
• Functional Keywords: sugar metabolism, protein-inhibitor complex, transferase
• Biological source: Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440)
• Cellular location: Cytoplasm: Q58999
• Total number of polymer chains: 3
• Total formula weight: 161089.93

Authors

Wisniewska, M.,Tokarz, P.,Grudnik, P. (deposition date: 2017-07-04, release date: 2018-01-31, Last modification date: 2024-01-17)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.98 Å)