Glycoside Hydrolase family classification


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

Non-Classified Sequences

- GH SubFamily Number


- GH Classification Statistics

Modules in present families 1750197
Non-Classified modules 50344

- 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 86 113 128 140 147 148 157 158 164 167 169 173
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 62 117
GH-G(α/α)637 63 100
GH-H(β/α)813 70 77
GH-Iα+β24 80
GH-J5-fold β-propeller32 68
GH-K(β/α)818 20 85
GH-L(α/α)615 65 125 178
GH-M(α/α)68 48
GH-Nβ-helix28 49
GH-O(α/α)652 116
GH-P(α/α)6127 146
GH-Q(α/α)694 149 161
GH-R(β/α)829 107
GH-S(α/α)6144 162
GH-T(β/α)757 119


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


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

[2Henrissat 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].

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

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

[5Terwisscha 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].

[6Rajan 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].

[7Liu 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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