GlycosylTransferase family classification


The biosynthesis of disaccharides, oligosaccharides and polysaccharides involves the action of hundreds of different glycosyltransferases (GTs) (EC 2.4.x.y), the enzymes that catalyse the transfer of sugar moieties from activated donor molecules to specific acceptor molecules, forming glycosidic bonds. Glycosyltransferases can be classified as either retaining or inverting enzymes according to the stereochemistry of the substrates and reaction products [1]. The recommendations of the International Union of Biochemistry and Molecular Biology (IUBMB) do not indicate the intrinsic structural features of the enzymes, nor do they adequately accommodate enzymes which act on several distinct substrates.

The CAZy database proposes the continuously updated classification of glycosyltransferases using nucleotide diphospho-sugar, nucleotide monophospho-sugars and sugar phosphates (EC 2.4.1.x) and related proteins into distinct sequence-based families as first described by Campbell et al. [2] and then by Coutinho et al. [3]. The same three-dimensional fold is expected to occur within each of the families. Just as for the glycoside hydrolases, several of the families defined on the basis of sequence similarities turn out to have similar three-dimensional structures. Polyspecificity (enzymes with different donor and/or acceptor found in the same family) is common among glycosyltransferase families, making precise functional predictions often unreliable or inaccurate.

Catalytic Mechanism

By analogy with glycosidases, two main stereochemical outcomes exist for glycosyltransferases : inversion of the anomeric configuration (for instance UDP-glucose -> β-glucoside) or retention of the anomeric configuration (for instance UDP-glucose -> α-glucoside).

Inverting glycosyltransferases most likely follow a single displacement mechanism where the acceptor performs a nucleophilic attack at carbon C-1 of the sugar donor somewhat anologous to the mechanism of inverting glycosidases. On the other hand, retaining glycosyltransferases do not appear to operate via a two-step mechanism involving the formation of a glycosyl-enzyme intermediate analogous to glycosidases. Instead, an internal return SNi-like mechanism has been proposed, in which leaving group departure and nucleophilic attack occur in a concerted but asynchronous manner on the same face of the glycoside [4].


[1Sinnott, M.L. (1990) Catalytic mechanisms of enzymatic glycosyl transfer. Chem. Rev. 90, 1171-1202.

[2Campbell JA, Davies GJ, Bulone V, Henrissat B (1997) A classification of nucleotide-diphospho-sugar glycosyltransferases based on amino acid sequence similarities. Biochem. J. 326:929-939 [PMID : 9334165].

[3Coutinho PM, Deleury E, Davies GJ, Henrissat B (2003) An evolving hierarchical family classification for glycosyltransferases. J. Mol. Biol. 328:307-317 [PMID : 12691742].

[4Lairson LL, Henrissat B, Davies GJ, Withers SG (2008) Glycosyltransferases : structures, functions, and mechanisms. Annu Rev Biochem. 77:521-555[PMID : 18518825].

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