The ADP‐dependent sugar kinase family: Kinetic and evolutionary aspects

Abstract

SummarySome archaea of the Euryarchaeota present a unique version of the Embden-Meyerhof pathway where glucose and fructose-6-phosphate are phoshporylated using ADP instead of ATP as the phosphoryl donor. These are the only ADP-dependent kinases known to date. Although initially they were believed to represent a new protein family, they can be classified as members of the ribokinase superfamily, which also include several ATP-dependent kinases. As they were first identified in members of the thermococcales it was proposed that the presence of these ADP-dependent kinases is an adaptation to high temperatures. Later, homologs of these enzymes were identified in the genomes of mesophilic and thermophilic methanogenic archaea and even in the genomes of higher eukaryotes, suggesting that the presence of these proteins is not related to the hyperthermophilic life. The ADP-dependent kinases are very restrictive to their ligands being unable to use triphosphorylated nucleotides such as ATP. However, it has been shown that they can bind ATP by competition kinetic experiments. The hyperthermophilic methanogenic archaeon Methanocaldococcus jannaschii has a homolog of these genes, which can phosphorylate glucose and fructose-6-phosphate. For this reason, it was proposed as an ancestral form for the family. However, recent studies have shown that the ancestral activity in the group is glucokinase, and a combination of gene duplication and lateral gene transfer could have originated the two paralogs in this member of the Euryarchaeota. Interestingly, based on structural comparisons made within the superfamily it has been suggested that the ADP-dependent kinases are the newest in the group. In several members of the superfamily, the presence of divalent metal cations has been shown to be crucial for catalysis, so its role in the ADP-dependent family was investigated through molecular dynamics. The simulation shows that, in fact, the metal coordinates the catalytic ensemble and interacts with crucial residues for catalysis. Keywords ADP-dependent kinase family; ribokinase superfamily; modified Embden-Meyerhof pathway; glucokinase; phosphofructokinase.Abbreviations ADP-GK, ADP-dependent glucokinase; ADP-PFK, ADP-dependent phosphofructokinase; ThzK, 4-Methyl-5-b-hydroxyethylthiazole kinase; HmppK, 4-amino-5-hydroxymethyl-2-methylpyrimidine kinase.

Carbohydrate Metabolism in Archaea: Current Insights into Unusual Enzymes and Pathways and Their Regulation

“…Archaeal ADP-GLKs prefer ADP as the phosphoryl donor and additionally also utilize CDP but not GDP, IDP, or UDP (57). The Arc.…”

“…The smaller domain, which covers the active site, forms an ␣/␤ two-layer structure containing 5 to 7 ␤ strands and 4 ␣ helices on the far side of the active-site cleft of the sheet (56,(59)(60)(61). The large domain represents the ribokinase core fold, which typically consists of an eight-stranded ␤ sheet surrounded by eight ␣ helices, three on one side and five on the other side of the sheet (57). Upon sugar binding, the small domain undergoes a conformational change, closing the active site (59,61).…”

“…Upon sugar binding, the small domain undergoes a conformational change, closing the active site (59,61). Although the "classical" hexokinases in Eukarya have been described to possess a similar two-domain architecture and to follow a comparable catalytic mechanism, there are no similarities between ADP-GLKs and hexokinases either on the sequence level or in the fold of both domains (44,45,57). ADP-GLKs contain two sequence motifs, i.e., GXGD and NXXE, highly conserved in members of the ribokinase superfamily and involved in catalysis (57).…”

Extremely Conserved ATP- or ADP-dependent Enzymatic System for Nicotinamide Nucleotide Repair

“…YKL151C was indeed the top candidate in terms of SEQUEST identification score in the list of proteins identified in the excised gel band. YKL151C belongs to the carbohydrate kinase family, which is part of the ribokinase superfamily (12). The latter comprises enzymes that phosphorylate a hydroxyl group of a substrate at the expense of ATP (e.g.…”

Development of an Electrochemical Adenosine Diphosphate (ADP) Sensing Principle Employing ADP-dependent Kinase

“…(8)(9)(10)(11)(12) These enzymes are known as ADP-dependent kinases. By focusing on the unique reactions that are catalyzed by this group of enzymes, some enzymatic assays have been already developed.…”