Glycoside hydrolase



  Glycoside hydrolases (also called glycosidases) glycosyltransferases, glycosidases form the major catalytic machinery for the synthesis and breakage of glycosidic bonds.


Occurrence and importance

Glycoside hydrolases are found in essentially all domains of life. In bacteria and prokaryotes, they are found both as intracellular and extracellular enzymes largely involved in nutrient acquisition. One of the important occurrences of glycoside hydrolases in bacteria is the enzyme beta-galactosidase (LacZ), which is involved in regulation of expression of the glycogen in the body.

Classification

Glycoside hydrolases are classified into EC 3.2.1 as enzymes catalyzing the hydrolysis of O- or S-glycosides. Glycoside hydrolases can also be classified according to the stereochemical outcome of the hydrolysis reaction: thus they can be classified as either retaining or inverting enzymes.[1] Glycoside hydrolases can also be classified as exo or endo acting, dependent upon whether they act at the (usually non-reducing) end or in the middle, respectively, of an oligo/polysaccharide chain. Glycoside hydrolases may also be classified by sequence based methods.

Sequence-based classification

Sequence-based classifications are among the most powerful predictive method for suggesting function for newly sequenced enzymes for which function has not been biochemically demonstrated. A classification system for glycosyl hydrolases, based on sequence similarity, has led to the definition of 85 different families[2][3][4]. This classification is available on the CAZy(CArbohydrate-Active EnZymes) web site[5]. The database provides a series of regularly updated sequence based classification that allow reliable prediction of mechanism (retaining/inverting), active site residues and possible substrates. Based on three dimensional structural similarities, the sequence-based families have been classified into 'clans' of related structure. Recent progress in glycosidase sequence analysis and 3D structure comparison has allowed the proposal of an extended hierarchical classification of the glycoside hydrolases.[6]

Mechanisms

Inverting glycoside hydrolases

Inverting enzymes utilize two enzymic residues, typically carboxylate residues, that act as base respectively, as shown below for a β-glucosidase:


Retaining glycoside hydrolases

Retaining glycosidases operate through a two-step mechanism, with each step resulting in lysozyme.[7]


An alternative mechanism for hydrolysis with retention of stereochemistry can occur that proceeds through a nucleophilic residue that is bound to the substrate, rather than being attached to the enzyme. Such mechanisms are common for certain N-acetylhexosaminidases, which have an acetamido group capable of neighboring group participation to form an intermediate oxazoline or oxazolinium ion. Again, the mechanism proceeds in two steps through individual inversions to lead to a net retention of configuration.


Nomenclature and examples

Glycoside hydrolases are typically named after the substrate that they act upon. Thus glucosidases catalyze the hydrolysis of glucosides and xylanases catalyze the cleavage of the xylose based homopolymer xylan. Other examples include lysozyme.

Uses

Glycoside hydrolases have a variety of uses including degradation of plant materials (eg cellulases for degrading cellulose to glucose, which can be used for amylase for production of maltodextrins), and in the paper and pulp industry (xylanases for removing hemicelluloses from paper pulp). Cellulases are added to detergents for the washing of cotton fabrics and assist in the maintenance of colours through removing microfibres that are raised from the surface of threads during wear.

In catalysts to form glycosidic bonds through either reverse hydrolysis (kinetic approach) where the equilibrium position is reversed; or by transglycosylation (kinetic approach) whereby retaining glycoside hydrolases can catalyze the transfer of a glycosyl moiety from an activated glycoside to an acceptor alcohol to afford a new glycoside.

Mutant glycoside hydrolases termed glycosynthases have been developed that can achieve the synthesis of glycosides in high yield from activated glycosyl donors such as glycosyl fluorides.

Inhibitors

Mnay compounds are known that can act to inhibit the action of a glycoside hydrolase. A number of nitrogen-containing 'sugar-shaped' heterocycles have been found in nature including deoxynojirimycin, swainsonine, australine and castanospermine. From these natural templates many other inhibitors have been developed including isofagomine and deoxygalactonojirimycin, and various unsaturated compounds such as PUGNAc. Several drugs in clinical use are inhbitors of glycoside hydrolases including miglitol and Tamiflu (oseltamivir). Some proteins have been fouind to act as glycoside hydrolase inhibitors.

See also

References

  1. ^ Sinnott, M. L. Chem. Rev. 1990, 90, 1171-1202.
  2. ^ Henrissat B, Callebaut I, Mornon JP, Fabrega S, Lehn P, Davies G (1995). "Conserved catalytic machinery and the prediction of a common fold for several families of glycosyl hydrolases". Proc. Natl. Acad. Sci. U.S.A. 92 (15): 7090-7094. PMID 7624375.
  3. ^ Henrissat B, Davies G (1995). "Structures and mechanisms of glycosyl hydrolases". Structure 3 (9): 853-859. PMID 8535779.
  4. ^ Bairoch A (1999). "Classification of glycosyl hydrolase families and index of glycosyl hydrolase entries in SWISS-PROT": -.
  5. ^ Henrissat B, Coutinho PM (1999). "Carbohydrate-Active Enzymes server": -.
  6. ^ Naumoff, D.G. Proceedings of the Fifth International Conference on Bioinformatics of Genome Regulation and Structure. 2006, 1, 294-298.
  7. ^ Vocadlo, D. J.; Davies, G. J.; Laine, R.; Withers, S. G. Nature 2001, 412, 835.
v • d • e
EC number
list
v • d • e
Lactase) - Cellulase, Alpha-glucosidase, Beta-glucosidase, Debranching enzyme)
3.2.2: Hydrolysing N-Glycosyl compoundsDNA glycosylases: Oxoguanine glycosylase
 
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