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of 4 - amino - 5 - hydroximethyl - 2 - methylpyrimidine phosphate kinase from Salmonella typhimurium at 2 . 3 Å resolution
Some 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. © 2009 IUBMB IUBMB Life, 61(7): 753–761, 2009
IUBMB Life – Wiley
Published: Jul 1, 2009
Keywords: ADP‐dependent kinase family; ribokinase superfamily; modified Embden–Meyerhof pathway; glucokinase; phosphofructokinase
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