Updating the sequence-based classification of glycosyl hydrolases

Biochem J , Pt 3 , 01 Aug Henrissat B. Biochem J , Pt 2 , 01 Dec Davies G , Henrissat B. Structure , 3 9 , 01 Sep Contact us. Europe PMC requires Javascript to function effectively. Recent Activity. Search life-sciences literature Over 39 million articles, preprints and more Search Advanced search. Henrissat B ,. Bairoch A. Share this article Share with email Share with twitter Share with linkedin Share with facebook. Abstract No abstract provided. Free full text. Biochem J. B Henrissat and A Bairoch.

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The number of the statements may be higher than the number of citations provided by EuropePMC if one paper cites another multiple times or lower if scite has not yet processed some of the citing articles. Explore citation contexts and check if this article has been supported or disputed. Functional glyco-metagenomics elucidates the role of glycan-related genes in environments. Some glycoside hydrolases are multifunctional enzymes that contain catalytic domains that belong to different GH families.

Structure [PMID: ]. Evidence for substrate assisted catalysis. Biochemistry [PMID: ]. Nature Biotechnol. Carbohydrate-Binding Modules. Introduction Archaea Bacteria Eukaryota Viruses. Introduction Glycoside hydrolases EC 3. For an updated table of glycoside hydrolase clans see the CAZy Database [ 4 ]. Two reaction mechanisms are most commonly found for the retaining and inverting enzymes, as first outlined by Koshland and as described below [ 9 ].

However several interesting variations on these mechanisms have been found, and one fundamentally different mechanism, catalyzed by an NADH cofactor, has been discovered in recent years.

Hydrolysis of a glycoside with net inversion of anomeric configuration is generally achieved via a one step, single-displacement mechanism involving oxocarbenium ion -like transition states , as shown below. The reaction typically occurs with general acid and general base assistance from two amino acid side chains, normally glutamic or aspartic acids, that are typically located A apart[ 10 ].

In these enzymes the usual general acid glutamic acid found in other members of this family is replaced by a glutamine. It has been suggested that the phosphate aglycon is a sufficiently good leaving group to be able to cleave in the first glycosylation step to form the glycosyl enzyme intermediate without the requirement of an acid catalyst [ 11 ]. This replacement may also reduce charge repulsion between the glutamic acid residue and the anionic phosphate aglycon. A related example may be found in the case of the family GH1 myrosinases.

Hydrolysis with net retention of configuration is most commonly achieved via a two step, double-displacement mechanism involving a covalent glycosyl-enzyme intermediate , as is shown in the figure below. Each step passes through an oxocarbenium ion -like transition state. In the first step often called the glycosylation step , one residue plays the role of a nucleophile, attacking the anomeric centre to displace the aglycon and form a glycosyl enzyme intermediate. At the same time the other residue functions as an acid catalyst and protonates the glycosidic oxygen as the bond cleaves.

In the second step known as the deglycosylation step , the glycosyl enzyme is hydrolyzed by water, with the other residue now acting as a base catalyst deprotonating the water molecule as it attacks. In the case of sialidases, the catalytic nucleophile is a tyrosine residue see below. This mechanism was originally proposed by Dan Koshland, although at the time the identities of the residues was unclear [ 9 ]. Enzymes of glycoside hydrolase families 18 , 20 , 25 , 56 , 84 , and 85 hydrolyse substrates containing an N -acetyl acetamido or N -glycolyl group at the 2-position.

These enzymes have no catalytic nucleophile: rather they utilize a mechanism in which the 2-acetamido group acts as an intramolecular nucleophile. Neighboring group participation by the 2-acetamido group leads to formation of an oxazoline or more strictly an oxazolinium ion intermediate.

This mechanism was deduced from X-ray structures of complexes of chitinases with natural inhibitors [ 13 ], from the potent inhibition afforded by a stable thiazoline analogue of the oxazoline [ 14 , 15 ], and from detailed mechanistic analyses using substrates of modified reactivity [ 16 ]. Typically, a stabilizing residue a carboxylate stabilizes the charge development in the transition state. Not all enzymes that cleave substrates possessing a 2-acetamido group utilize a neighboring groups participation mechanism; enzyme of glycoside hydrolase families 3 and 22 utilize a classical retaining mechanism with an enzymic nucleophile.

Other hexosaminidases such as those of Glycoside Hydrolase Family 19 utilize an inverting mechanism. Glycoside hydrolases termed myrosinases catalyze the hydrolysis of anionic thioglycosides glucosinolates found in plants. They are found in Glycoside Hydrolase Family 1.