GlycosylTransferase family classification

Introduction

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].

Tables for Direct Access

- GT Family Number

12345678910111213141516171819202122232425262728293031323334353637383940
41424344454647484950515253545556575859606162636465666768697071727374757677787980
81828384858687888990919293949596979899100101102103104105
Non-Classified Sequences

- GT Classification Statistics

Modules in present families 371482
Non-Classified modules 8025

- EC Activities found in GT families

Caution : Because of the modular nature of CAZymes, these activities may not be directly associated with the family but simply borne by adjacent modules.

2.-.-.- 1 9 20
2.4.-.- 1 43 51 NC
2.4.1.- 1 2 4 5 7 8 10 11 13 14 21 22 23 24 25 26 28 29 31 32 33 34 37 40 41 44 45
2.4.1.1 35
2.4.1.11 3 5
2.4.1.12 2
2.4.1.13 4
2.4.1.14 4
2.4.1.15 20
2.4.1.16 2
2.4.1.17 1 2 70
2.4.1.21 4 5
2.4.1.22 7
2.4.1.26 72
2.4.1.27 63
2.4.1.34 2 48
2.4.1.37 6 77
2.4.1.38 7
2.4.1.40 6
2.4.1.41 27
2.4.1.44 8
2.4.1.45 1
2.4.1.46 1 28
2.4.1.47 1
2.4.1.50 25
2.4.1.52 4
2.4.1.56 4 9 99 102 103
2.4.1.57 4
2.4.1.58 8
2.4.1.65 10
2.4.1.66 NC
2.4.1.68 23
2.4.1.69 2 11 37 74
2.4.1.79 31
2.4.1.80 21 NC
2.4.1.83 2
2.4.1.87 6
2.4.1.88 6
2.4.1.90 7
2.4.1.91 1
2.4.1.92 12
2.4.1.101 13
2.4.1.102 14
2.4.1.109 39 105
2.4.1.115 1
2.4.1.117 2
2.4.1.120 1
2.4.1.121 1
2.4.1.122 31
2.4.1.123 8
2.4.1.128 1
2.4.1.129 51
2.4.1.131 4 15
2.4.1.132 4
2.4.1.133 7
2.4.1.134 31
2.4.1.135 43
2.4.1.142 33
2.4.1.143 16
2.4.1.144 17
2.4.1.145 54
2.4.1.149 31 67
2.4.1.150 14
2.4.1.152 10
2.4.1.155 18
2.4.1.157 2 4 28
2.4.1.159 1
2.4.1.170 1
2.4.1.173 1
2.4.1.174 7
2.4.1.175 2 7 31
2.4.1.177 1
2.4.1.182 19
2.4.1.183 5
2.4.1.185 1
2.4.1.186 8
2.4.1.189 1
2.4.1.194 1
2.4.1.195 1
2.4.1.198 4
2.4.1.199 2
2.4.1.203 1
2.4.1.208 4
2.4.1.210 1
2.4.1.212 2
2.4.1.213 20
2.4.1.214 10
2.4.1.215 1
2.4.1.217 55 78 81
2.4.1.221 65
2.4.1.222 31
2.4.1.223 47 64
2.4.1.224 47 64
2.4.1.225 47 64
2.4.1.226 2 7 31
2.4.1.227 28
2.4.1.231 4
2.4.1.234 1
2.4.1.237 1
2.4.1.238 1
2.4.1.241 4 28
2.4.1.242 5
2.4.1.245 4
2.4.1.251 94
2.4.1.252 4
2.4.1.253 1
2.4.1.255 41 61
2.4.1.256 59
2.4.1.257 4 32 62
2.4.1.258 58
2.4.1.259 22
2.4.1.260 22
2.4.1.261 22
2.4.1.275 7
2.4.1.283 4
2.4.1.285 4
2.4.1.286 1
2.4.1.287 2
2.4.1.288 2
2.4.1.289 2 99 102 103
2.4.1.290 4
2.4.1.305 2
2.4.1.342 4
2.4.2.- 1 2 4 8 25 43 47 49 53 61 77 79 85 89 90 95 NC
2.4.2.26 14
2.4.2.38 61
2.4.2.39 34
2.4.2.40 1
2.4.2.43 83
2.4.99.- 1 4 9 29 30 38 42 73 97 99 100 102 103 NC
2.4.99.1 29 52 80
2.4.99.3 29 42
2.4.99.4 29 42 52 80
2.4.99.6 29 42 52
2.4.99.7 29
2.4.99.8 29 42
2.4.99.9 29
2.4.99.18 66
2.4.99.19 66
3.1.3.12 20
3.2.1.- 80
3.2.1.18 80
3.5.1.- 4
5.4.99.- 75

Footnotes

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

[2 Campbell 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].

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

[4 Lairson 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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