5od2

Publication Abstract from PubMed

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 beta-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. This article is protected by copyright. All rights reserved.

Crystal structure of ADP-dependent glucokinase from Methanocaldococcus jannaschii in complex with 5-iodotubercidin reveals phosphoryl transfer mechanism.,Tokarz P, Wisniewska M, Kaminski MM, Dubin G, Grudnik P Protein Sci. 2018 Jan 20. doi: 10.1002/pro.3377. PMID:29352744^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.