Guixé Victoria, Merino Felipe
Departamento de Biología, Facultad de Ciencias, Universidad de Chile, Casilla 653, Santiago, Chile.
IUBMB Life. 2009 Jul;61(7):753-61. doi: 10.1002/iub.217.
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.
广古菌门的一些古菌呈现出一种独特版本的糖酵解途径（Embden-Meyerhof pathway），其中葡萄糖和6-磷酸果糖是利用ADP而非ATP作为磷酰基供体进行磷酸化的。这些是迄今为止已知的仅有的依赖ADP的激酶。尽管最初它们被认为代表一个新的蛋白质家族，但它们可被归类为核糖激酶超家族的成员，该超家族还包括几种依赖ATP的激酶。由于它们最初是在嗜热栖热菌属（Thermococcales）的成员中被鉴定出来的，因此有人提出这些依赖ADP的激酶的存在是对高温的一种适应。后来，在嗜温及嗜热产甲烷古菌的基因组中甚至在高等真核生物的基因组中都鉴定出了这些酶的同源物，这表明这些蛋白质的存在与超嗜热生活无关。依赖ADP的激酶对其配体具有很强的选择性，无法使用三磷酸化核苷酸如ATP。然而，通过竞争动力学实验已表明它们能够结合ATP。超嗜热产甲烷古菌詹氏甲烷球菌（Methanocaldococcus jannaschii）有这些基因的一个同源物，它能够使葡萄糖和6-磷酸果糖磷酸化。因此，它被提议作为该家族的一种原始形式。然而，最近的研究表明该类群中的原始活性是葡萄糖激酶，基因复制和横向基因转移的结合可能产生了广古菌门这个成员中的两个旁系同源物。有趣的是，基于在超家族内进行的结构比较，有人提出依赖ADP的激酶是该类群中最新的成员。在超家族的几个成员中，已表明二价金属阳离子的存在对催化至关重要，因此通过分子动力学研究了其在依赖ADP的家族中的作用。模拟表明，实际上，金属协调催化组件并与催化关键残基相互作用。
