Glycoside Hydrolase family classification

Introduction

Glycoside hydrolases (EC 3.2.1.-) are a widespread group of enzymes which hydrolyse the glycosidic bond between two or more carbohydrates or between a carbohydrate and a non-carbohydrate moiety. The IUBMB Enzyme nomenclature of glycoside hydrolases is based on their substrate specificity and occasionally on their molecular mechanism; such a classification does not reflect (and was not intended to) the structural features of these enzymes. A classification of glycoside hydrolases in families based on amino acid sequence similarities has been proposed a few years ago. Because there is a direct relationship between sequence and folding similarities, such a classification:

(i) reflects the structural features of these enzymes better than their sole substrate specificity,

(ii) helps to reveal the evolutionary relationships between these enzymes,

(iii) provides a convenient tool to derive mechanistic information [1] [2]

(iv) illustrates the difficulty of deriving relationships between family membership and substrate specificity

The Carbohydrate-Active Enzymes database (CAZy) provides a continuously updated list of the glycoside hydrolase families. Because the fold of proteins is better conserved than their sequences, some of the families can be grouped in ’clans’ :
(i) when new sequences are found to be related to more than one family,
(ii) when the sensitivity of sequence comparison methods is increased or
(iii) when structural determinations demonstrate the resemblance between members of different families [3]

The established ’clans’ are given in form of a table below.

Catalytic Mechanism

In most cases, the hydrolysis of the glycosidic bond is catalyzed by two amino acid residues of the enzyme: a general acid (proton donor) and a nucleophile/base [4]. Depending on the spatial position of these catalytic residues, hydrolysis occurs via overall retention or overall inversion of the anomeric configuration. For each family listed in the CAZy database, we indicate (when it is known) the stereochemical outcome of the reaction catalyzed as well as the type of amino-acid residues acting as a nucleophile/base and as a proton donor. In some cases, the catalytic nucleophile is not borne by the enzyme, and is replaced by the acetamido group at C-2 of the substrate [5]. A completely unrelated mechanism has been demonstrated recently for two families of glycosidases utilizing NAD+ as a cofactor [6] [7].

For a detailed description of the catalytic mechanism (and variations thereof) of glycoside hydrolases, please visit CAZypedia.

Tables for Direct Access

- GH Family Number

12345678910111213141516171819202122232425262728293031323334353637383940
41424344454647484950515253545556575859606162636465666768697071727374757677787980
81828384858687888990919293949596979899100101102103104105106107108109110111112113114115116117118119120
121122123124125126127128129130131132133
Non-Classified Sequences

- GH Classification Statistics

Modules in present families 207780
Non-Classified modules 2512

- GH Clans of Related Families

GH-A(β/α)81 2 5 10 17 26 30 35 39 42 50 51 53 59 72 79 86 113 128
GH-Bβ-jelly roll7 16
GH-Cβ-jelly roll11 12
GH-D(β/α)827 31 36
GH-E6-fold β-propeller33 34 83 93
GH-F5-fold β-propeller43 62
GH-G(α/α)637 63
GH-H(β/α)813 70 77
GH-Iα+β24 46 80
GH-J5-fold β-propeller32 68
GH-K(β/α)818 20 85
GH-L(α/α)615 65 125
GH-M(α/α)68 48
GH-Nβ-helix28 49

- EC Activities found in GH 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.

2.4.1.- 1 5 13 16 17 20 27 31 32 33 35 65 70 72 94 112 130
2.4.1.4 13
2.4.1.5 70
2.4.1.7 13
2.4.1.8 65
2.4.1.9 68
2.4.1.10 32 68
2.4.1.12 6
2.4.1.18 13 57
2.4.1.19 13
2.4.1.20 94
2.4.1.25 13 57 77 133
2.4.1.31 94
2.4.1.49 94
2.4.1.64 65
2.4.1.67 36
2.4.1.82 36
2.4.1.99 32
2.4.1.100 32
2.4.1.140 70
2.4.1.161 31
2.4.1.183 13
2.4.1.207 12 16
2.4.1.211 112
2.4.1.216 65
2.4.1.230 65
2.4.1.243 32
2.4.1.247 112
2.4.1.248 66
2.4.1.279 65
2.4.1.281 130
2.4.1.282 65
2.4.2.- 10
2.4.99.16 13
3.1.1.- 5
3.1.1.72 5 11
3.1.1.73 10 78
3.2.1.- 1 2 3 4 5 9 10 13 16 17 18 19 20 26 28 30 32 33 35 38 42 43 44 56 57 63 67
3.2.1.1 13 14 57 119
3.2.1.2 13 14
3.2.1.3 15 97
3.2.1.4 5 6 7 8 9 10 12 26 44 45 48 51 74 124 NC
3.2.1.6 9 16
3.2.1.7 32
3.2.1.8 5 8 9 10 11 12 16 26 30 43 44 51 62
3.2.1.10 13 31
3.2.1.11 49 66
3.2.1.14 18 19 23 48 NC
3.2.1.15 28
3.2.1.17 18 19 22 23 24 25 73 108 NC
3.2.1.18 1 33 34 83 NC
3.2.1.20 4 13 31 63 97 122 NC
3.2.1.21 1 3 5 9 30 116 NC
3.2.1.22 4 27 36 57 97 110
3.2.1.23 1 2 3 35 42 50 59 NC
3.2.1.24 31 38 92
3.2.1.25 1 2 5
3.2.1.26 32 68 100
3.2.1.28 13 15 37 65
3.2.1.31 1 2 30 79
3.2.1.32 10 11 26
3.2.1.33 13 133
3.2.1.35 16 56 84
3.2.1.36 79
3.2.1.37 1 3 5 30 39 43 51 52 54 116 120
3.2.1.38 1 3 30 35
3.2.1.39 16 17 55 64 81 128 NC
3.2.1.40 13 78 106
3.2.1.41 13 57
3.2.1.45 3 5 30 116
3.2.1.46 59
3.2.1.48 31
3.2.1.49 27 36 109 129
3.2.1.50 89
3.2.1.51 29 95 NC
3.2.1.52 3 5 18 20 84 116 NC
3.2.1.54 13 57
3.2.1.55 2 3 10 43 51 54 62
3.2.1.57 49
3.2.1.58 3 5 17 55
3.2.1.59 71 87
3.2.1.60 13
3.2.1.61 87
3.2.1.62 1
3.2.1.63 95
3.2.1.64 32
3.2.1.65 32
3.2.1.67 4 28
3.2.1.68 13
3.2.1.70 13 15
3.2.1.73 5 7 8 9 11 12 16 17 26
3.2.1.74 1 3 5 9
3.2.1.75 5 30
3.2.1.76 39
3.2.1.78 5 9 26 44 113
3.2.1.80 32
3.2.1.81 16 50 86 118
3.2.1.82 28
3.2.1.83 16
3.2.1.84 31 63
3.2.1.85 1
3.2.1.86 1 4
3.2.1.88 27
3.2.1.89 53
3.2.1.91 5 6 9
3.2.1.93 13
3.2.1.94 27
3.2.1.95 49
3.2.1.96 18 20 73 85
3.2.1.97 101
3.2.1.98 13
3.2.1.99 43
3.2.1.100 26
3.2.1.101 76
3.2.1.102 98
3.2.1.103 16
3.2.1.104 5
3.2.1.105 1
3.2.1.106 63
3.2.1.108 1
3.2.1.109 114
3.2.1.111 29
3.2.1.113 38 47 92
3.2.1.114 38
3.2.1.116 13
3.2.1.117 1
3.2.1.118 1
3.2.1.119 1
3.2.1.120 3
3.2.1.122 4
3.2.1.123 5
3.2.1.125 1
3.2.1.126 3
3.2.1.129 58
3.2.1.130 99
3.2.1.131 67 115
3.2.1.132 3 5 7 8 46 75 80
3.2.1.133 13
3.2.1.135 13
3.2.1.136 30
3.2.1.139 4 67
3.2.1.140 20 NC
3.2.1.141 13
3.2.1.145 43
3.2.1.147 1
3.2.1.149 1 5
3.2.1.150 74
3.2.1.151 5 9 12 16 26 44 74
3.2.1.152 2
3.2.1.153 32
3.2.1.154 32
3.2.1.156 8
3.2.1.157 82
3.2.1.158 96
3.2.1.161 1
3.2.1.164 5 30
3.2.1.165 2 9 35
3.2.1.166 79
3.2.1.167 79
3.2.1.169 84
3.2.1.170 38 63
3.2.1.171 28
3.2.1.172 105
3.2.1.173 28
3.2.1.174 28
3.2.1.175 1 17
3.2.1.176 7 9 48
3.2.1.177 31
3.2.1.178 16 86
3.2.1.181 16
3.2.1.182 1
3.2.1.185 127
3.5.2.17 1
4.2.2.n1 23 102 103 104
4.2.2.13 31
4.2.2.16 32
4.2.2.17 91
4.2.2.18 91
5.4.99.11 13
5.4.99.15 13
5.4.99.16 13

Note

Some glycoside hydrolases are multifunctional enzymes that contain catalytic domains that belong to different GH families.

Footnotes

[1 Henrissat B (1991) A classification of glycosyl hydrolases based on amino-acid sequence similarities. Biochem. J. 280:309-316 [PMID: 1747104].

[2 Henrissat B, Bairoch A (1993) New families in the classification of glycosyl hydrolases based on amino- acid sequence similarities. Biochem. J. 293:781-788 [PMID: 8352747].

[3 Henrissat B, Bairoch A (1996) Updating the sequence-based classification of glycosyl hydrolases. Biochem. J. 316:695-696 [PMID: 8687420].

[4 Davies G, Henrissat B (1995) Structures and mechanisms of glycosyl hydrolases. Structure 3:853-859 [PMID: 8535779].

[5 Terwisscha van Scheltinga A, Armand S, Kalk KH, Isogai A, Henrissat B, Dijkstra BW (1995) Stereochemistry of chitin hydrolysis by a plant chitinase/lysozyme and x-ray structure of a complex with allosamidin. Evidence for substrate assisted catalysis. Biochemistry 34:15619-15623
[PMID: 7495789].

[6 Rajan SS, Yang X, Collart F, Yip VL, Withers SG, Varrot A, Thompson J, Davies GJ, Anderson WF (2004) Novel catalytic mechanism of glycoside hydrolysis based on the structure of an NAD+/Mn2+ -dependent phospho-alpha-glucosidase from Bacillus subtilis. Structure. 12:1619-1629
[PMID: 15341727].

[7 Liu QP, Sulzenbacher G, Yuan H, Bennett EP, Pietz G, Saunders K, Spence J, Nudelman E, Levery SB, White T, Neveu JM, Lane WS, Bourne Y, Olsson ML, Henrissat B, Clausen H (2007) Bacterial glycosidases for the production of universal red blood cells. Nature Biotechnol. 25:454-464
[PMID: 17401360].

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