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Sweet secrets of synthesis

Nature Structural Biology volume 8, pages 98–100 (2001)Cite this article

The crystal structure of a `retaining' glycosyltransferase provides the first view of α-glycosidic bond synthesis using activated nucleotide sugars.

These are exciting times for glycobiology. Simply in terms of quantity, the formation of glycosides such as di-, oligo- and polysaccharides and various glycoconjugates, is the most important biological reaction on earth. Yet despite their profound importance, the enzymes involved in this process — nucleotide-sugar dependent glycosyltransferases — have until recently remained one of the great uncharted areas of structural and mechanistic enzymology. On page 166 of this issue of Nature Structural Biology, however, Persson and colleagues1 reveal the structure of an enzyme that makes α-glycosidic linkages using activated α-linked nucleotide-sugar donors — a so-called `retaining' glycosyltransferase. The alpha-1,4-galactosyltransferase C (lgtC) from Neisseria meningitidis provides our first view of how nature synthesizes glycosidic linkages with retention of anomeric configuration. The structure determination and analysis involved the harnessing of specifically synthesized UDP-sugar and oligosaccharide analogs, site-directed mutagenesis and kinetics. This work has important ramifications for researchers in glycobiology, especially those in the quest for new therapeutic agents.

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Figure 1: Reaction mechanism for an inverting NDP-sugar glycosyltransferase.
Figure 2: Possible mechanisms for a retaining NDP-sugar glycosyltransferase.
Figure 3: The active center of lgtC is reminiscent of glycogen and maltodextrin phosphorylases.

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  1. the Department of Chemistry, Structural Biology Laboratory, University of York, Heslington, YO10 5DD, York, UK

    Gideon J. Davies

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Davies, G. Sweet secrets of synthesis. Nat Struct Mol Biol 8, 98–100 (2001). https://doi.org/10.1038/84198

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