Abstract
Carbohydrate kinases activate a wide variety of monosaccharides by adding a phosphate group, usually from ATP. This modification is fundamental to saccharide utilization, and it is likely a very ancient reaction. Modern organisms contain carbohydrate kinases from at least five main protein families. These range from the highly specialized inositol kinases, to the ribokinases and galactokinases, which belong to families that phosphorylate a wide range of substrates. The carbohydrate kinases utilize a common strategy to drive the reaction between the sugar hydroxyl and the donor phosphate. Each sugar is held in position by a network of hydrogen bonds to the non-reactive hydroxyls (and other functional groups). The reactive hydroxyl is deprotonated, usually by an aspartic acid side chain acting as a catalytic base. The deprotonated hydroxyl then attacks the donor phosphate. The resulting pentacoordinate transition state is stabilized by an adjacent divalent cation, and sometimes by a positively charged protein side chain or the presence of an anion hole. Many carbohydrate kinases are allosterically regulated using a wide variety of strategies, due to their roles at critical control points in carbohydrate metabolism. The evolution of a similar mechanism in several folds highlights the elegance and simplicity of the catalytic scheme.
Highlights
Carbohydrate kinases activate a wide variety of monosaccharides by adding a phosphate group, usually from ATP
The carbohydrate kinases utilize a common strategy to drive the reaction between the sugar hydroxyl and the donor phosphate
To HKs, ROK kinases catalyze the phosphorylation of carbohydrates using a conserved aspartic acid to act as a general base and deprotonate the reactive hydroxyl group [17,64]
Summary
Monosaccharides play a critical role in every organism on Earth [1]. They underpin energy generation and central metabolism, and they act as the building blocks for the biosynthesis of polysaccharides. Phosphorylation of sugars provides two negative charges that prevent passive diffusion across the cell membrane, enabling intracellular concentration of intermediates [4]. Phosphorylation at both terminal hydroxyls permits reactions that split saccharides, such as the aldolase-catalyzed retro-aldol reactions in glycolysis [5]. The reaction is performed by enzymes from five evolutionarily distinct classes (Table 1, Figure 1) These carbohydrate kinases transfer the terminal phosphate from a nucleoside triphosphate (usually ATP) to a free sugar hydroxyl [5]. Despite class has strong experimental evidence for enzyme specificity, regulation, and catalytic mechanism. This review shows how evolution has achieved the same outcome effectively different protein folds.
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