Abstract
Glycosyltransferases (GTs), the enzymes that catalyse glycosidic bond formation, create a diverse range of saccharides and glycoconjugates in nature. Understanding GTs at the molecular level, through structural and kinetic studies, is important for gaining insights into their function. In addition, this understanding can help identify those enzymes which are involved in diseases, or that could be engineered to synthesize biologically or medically relevant molecules. This review describes how structural data, obtained in the last 3-4 years, have contributed to our understanding of the mechanisms of action and specificity of GTs. Particular highlights include the structure of a bacterial oligosaccharyltransferase, which provides insights into N-linked glycosylation, the structure of the human O-GlcNAc transferase, and the structure of a bacterial integral membrane protein complex that catalyses the synthesis of cellulose, the most abundant organic molecule in the biosphere.
Highlights
Glycosyltransferases (GTs) are the ubiquitous enzymes responsible for creating the diverse and complex array of oligosaccharides and glycoconjugates found in nature
GTs have been classified by sequence homology into 96 families in the Carbohydrate Active enZyme database (CAZy) [1]
The structure reveals that two conserved aspartate residues coordinate UDP, and a third aspartate likely functions as the catalytic base
Summary
Glycosyltransferases (GTs) are the ubiquitous enzymes responsible for creating the diverse and complex array of oligosaccharides and glycoconjugates found in nature. The GT domain of BcsA adopts a GT-A fold comprising seven b-strands surrounded by seven a-helices, and contains signatures characteristic of processive GTs. The structure reveals that two conserved aspartate residues coordinate UDP, and a third aspartate (part of an invariant TED motif) likely functions as the catalytic base. Crystallographic snapshots of glycogenin at different stages of its catalytic cycle were captured, and demonstrated large conformational changes involving a 30 residue ‘lid’ that covers the active site, induced by UDP-Glc binding [44] This lid is important for guiding the oligosaccharide chain acceptor (either inter-molecularly or intra-molecularly) into the active site in the correct position for catalysis. The significant steps forward on several key GTs, for example those involved in N-linked glycosylation, the O-GlcNAc modification, and cellulose biosynthesis, represents a substantial advance for the field These structural breakthroughs underpin our understanding of the molecular details of these enzymes, which will impact on medical or biotechnological processes. The carbohydrate enzyme structural community should take heed that elucidating GT structures previously considered as the pinnacle of difficulty is possible, and is vital to furthering our understanding of this key class of enzyme
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