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

– GH SubFamily Number

– GH Classification Statistics

– GH Clans of Related Families