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Glycoside hydrolases (also called glycosidases or glycosyl hydrolases)
catalyze that utilizes a low-temperature oxidation catalyst to convert carbon monoxide to less toxic carbon dioxide Carbon dioxide (chemical formula ) is a colorless gas with a density about 53% higher than that of dry air. Carbon dioxide molecules ...

catalyze
the
hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution Substitution may refer to: Arts and media *Chord substitution, in music, swapping one chord fo ...

hydrolysis
of
glycosidic bonds A glycosidic bond or glycosidic linkage is a type of covalent bond A covalent bond is a chemical bond that involves the sharing of electron pairs between atoms. These electron pairs are known as shared pairs or bonding pairs, and the stable ...
in complex sugars. They are extremely common
enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates in ...

enzyme
s with roles in nature including degradation of
biomass Biomass is plant or animal material used as fuel to produce electricity Electricity is the set of physical phenomena associated with the presence and motion Image:Leaving Yongsan Station.jpg, 300px, Motion involves a change in position ...

biomass
such as
cellulose Cellulose is an organic compound In chemistry Chemistry is the study of the properties and behavior of . It is a that covers the that make up matter to the composed of s, s and s: their composition, structure, properties, behavior ...

cellulose
(
cellulase Cellulase is any of several enzymes Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, a ...
),
hemicellulose A hemicellulose (also known as polyose) is one of a number of heteropolymer, heteropolymers (matrix polysaccharides), such as arabinoxylans, present along with cellulose in almost all embryophyte, terrestrial plant cell walls.Scheller HV, Ulvskov H ...

hemicellulose
, and
starch Starch or amylum is a polymeric A polymer (; Greek '' poly-'', "many" + '' -mer'', "part") is a substance Substance may refer to: * Substance (Jainism), a term in Jain ontology to denote the base or owner of attributes * Chemical substance ...
(
amylase An amylase () is an enzyme Enzymes () are protein Proteins are large s and s that comprise one or more long chains of . Proteins perform a vast array of functions within organisms, including , , , providing and , and from one lo ...
), in anti-bacterial defense strategies (e.g.,
lysozyme Lysozyme, also known as muramidase or N-acetylmuramide glycanhydrolase, is an antimicrobial An antimicrobial is an agent that kills microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism In biology, an ...

lysozyme
), in
pathogenesis Pathogenesis is the process by which a disease A disease is a particular abnormal condition that negatively affects the structure A structure is an arrangement and organization of interrelated elements in a material object or system ...

pathogenesis
mechanisms (e.g., viral
neuraminidase Neuraminidase (Sialidase) enzymes are glycoside hydrolase 1HNY, a glycoside hydrolase Glycoside hydrolases (also called glycosidases or glycosyl hydrolases) catalysis, catalyze the hydrolysis Hydrolysis (; ) is any chemical reaction in whic ...

neuraminidase
s) and in normal cellular function (e.g., trimming mannosidases involved in N-linked glycoprotein
biosynthesis Biosynthesis is a multi-step, enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and ...

biosynthesis
). Together with
glycosyltransferase Glycosyltransferases (GTFs, Gtfs) are enzymes (Enzyme Commission number, EC 2.4) that establish natural glycosidic linkages. They catalyze the transfer of saccharide Moiety (chemistry), moieties from an activated nucleotide sugar (also known as th ...
s, 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
prokaryotes A prokaryote () is a single-celled organism A unicellular organism, also known as a single-celled organism, is an organism In biology, an organism (from Ancient Greek, Greek: ὀργανισμός, ''organismos'') is any individual contig ...

prokaryotes
, they are found both as intracellular and extracellular enzymes that are largely involved in nutrient acquisition. One of the important occurrences of glycoside hydrolases in bacteria is the enzyme
beta-galactosidase β-galactosidase, also called lactase, beta-gal or β-gal, is a family of glycoside hydrolase 1HNY, a glycoside hydrolase Glycoside hydrolases (also called glycosidases or glycosyl hydrolases) catalysis, catalyze the hydrolysis Hydrolysis (; ...

beta-galactosidase
(LacZ), which is involved in regulation of expression of the
''lac'' operon
''lac'' operon
in ''
E. coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative Gram-negative bacteria are bacteria Bacteria (; common noun bacteri ...

E. coli
''. In higher organisms glycoside hydrolases are found within the
endoplasmic reticulum The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...
and
Golgi apparatus The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle In cell biology Cell biology (also cellular biology or cytology) is a branch of biology Biology is the natural science that stu ...

Golgi apparatus
where they are involved in processing of N-linked
glycoproteins Glycoproteins are protein Proteins are large biomolecules or macromolecules that are comprised of one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including ...
, and in the
lysosome A lysosome () is a membrane-bound organelle found in many animal Cell (biology), cells. They are spherical Vesicle (biology and chemistry), vesicles that contain Hydrolysis, hydrolytic enzymes that can break down many kinds of biomolecules. A ly ...

lysosome
as enzymes involved in the degradation of carbohydrate structures. Deficiency in specific lysosomal glycoside hydrolases can lead to a range of lysosomal storage disorders that result in developmental problems or death. Glycoside hydrolases are found in the
intestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organ (biology), organs of the digestive syst ...
and in
saliva Saliva (commonly referred to as spit) is an extracellular fluid In cell biology Cell biology (also cellular biology or cytology) is a branch of biology Biology is the natural science that studies life and living organisms, including t ...
where they degrade complex carbohydrates such as
lactose Lactose, a disaccharide A disaccharide (also called a double sugar or ''biose'') is the sugar Sugar is the generic name for sweet-tasting, soluble carbohydrate is a disaccharide A disaccharide (also called a double sugar or ''biose ...

lactose
,
starch Starch or amylum is a polymeric A polymer (; Greek '' poly-'', "many" + '' -mer'', "part") is a substance Substance may refer to: * Substance (Jainism), a term in Jain ontology to denote the base or owner of attributes * Chemical substance ...
,
sucrose Sucrose is a type of sugar Sugar is the generic name for , soluble s, many of which are used in food. Simple sugars, also called s, include , , and . Compound sugars, also called s or double sugars, are molecules made of two monosacchari ...

sucrose
and trehalose. In the gut they are found as glycosylphosphatidyl anchored enzymes on endothelial cells. The enzyme lactase is required for degradation of the milk sugar lactose and is present at high levels in infants, but in most populations will decrease after weaning or during infancy, potentially leading to lactose intolerance in adulthood. The enzyme O-GlcNAcase is involved in removal of N-acetylglucosamine groups from serine and threonine residues in the cytoplasm and nucleus of the cell. The glycoside hydrolases are involved in the
biosynthesis Biosynthesis is a multi-step, enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and ...

biosynthesis
and degradation of 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. 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 or structure-based methods.CAZy Family Glycoside Hydrolase
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Sequence-based classification

Sequence-based classifications are one of the most powerful predictive methods 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 more than 100 different families. This classification is available on the CAZy (CArbohydrate-Active EnZymes) web site. 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. The online database is supported by CAZypedia, an online encyclopedia of carbohydrate active enzymes. 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.


Mechanisms


Inverting glycoside hydrolases

Inverting enzymes utilize two enzymic residues, typically carboxylate residues, that act as acid and base (chemistry), base respectively, as shown below for a beta-glucosidase, β-glucosidase:


Retaining glycoside hydrolases

Retaining glycosidases operate through a two-step mechanism, with each step resulting in Walden inversion, inversion, for a net retention of stereochemistry. Again, two residues are involved, which are usually enzyme-borne carboxylates. One acts as a nucleophile and the other as an acid/base. In the first step, the nucleophile attacks the anomeric centre, resulting in the formation of a glycosyl enzyme intermediate, with acidic assistance provided by the acidic carboxylate. In the second step, the now deprotonated acidic carboxylate acts as a base and assists a nucleophilic water to hydrolyze the glycosyl enzyme intermediate, giving the hydrolyzed product. The mechanism is illustrated below for hen egg white
lysozyme Lysozyme, also known as muramidase or N-acetylmuramide glycanhydrolase, is an antimicrobial An antimicrobial is an agent that kills microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism In biology, an ...

lysozyme
. 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. This mechanism proceeds in two steps through individual inversions to lead to a net retention of configuration. A variant neighboring group participation mechanism has been described for endo-α-mannanases that involves 2-hydroxyl group participation to form an intermediate epoxide. Hydrolysis of the epoxide leads 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 lactase,
amylase An amylase () is an enzyme Enzymes () are protein Proteins are large s and s that comprise one or more long chains of . Proteins perform a vast array of functions within organisms, including , , , providing and , and from one lo ...
, chitinase, sucrase, maltase,
neuraminidase Neuraminidase (Sialidase) enzymes are glycoside hydrolase 1HNY, a glycoside hydrolase Glycoside hydrolases (also called glycosidases or glycosyl hydrolases) catalysis, catalyze the hydrolysis Hydrolysis (; ) is any chemical reaction in whic ...

neuraminidase
, invertase, hyaluronidase and
lysozyme Lysozyme, also known as muramidase or N-acetylmuramide glycanhydrolase, is an antimicrobial An antimicrobial is an agent that kills microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism In biology, an ...

lysozyme
.


Uses

Glycoside hydrolases are predicted to gain increasing roles as catalysts in biorefining applications in the future bioeconomy. These enzymes have a variety of uses including degradation of plant materials (e.g., cellulases for degrading cellulose to glucose, which can be used for ethanol production), in the food industry (invertase for manufacture of invert sugar,
amylase An amylase () is an enzyme Enzymes () are protein Proteins are large s and s that comprise one or more long chains of . Proteins perform a vast array of functions within organisms, including , , , providing and , and from one lo ...
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 organic chemistry, glycoside hydrolases can be used as synthetic 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. Glycosynthases are typically formed from retaining glycoside hydrolases by site-directed mutagenesis of the enzymic nucleophile to some other less nucleophilic group, such as alanine or glycine. Another group of mutant glycoside hydrolases termed thioglycoligases can be formed by site-directed mutagenesis of the acid-base residue of a retaining glycoside hydrolase. Thioglycoligases catalyze the condensation of activated glycosides and various thiol-containing acceptors. Various glycoside hydrolases have shown efficacy in degrading matrix polysaccharides within the extracellular polymeric substance (EPS) of Biofilm, microbial biofilms. Medically, biofilms afford infectious microorganisms a variety of advantages over their planktonic, fre-floating counterparts, including greatly increased tolerances to antimicrobial agents and the host immune system. Thus, degrading the biofilm may increase antibiotic efficacy, and potentiate host immune function and healing ability. For example, a combination of alpha-amylase and
cellulase Cellulase is any of several enzymes Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, a ...
was shown to degrade polymicrobial bacterial biofilms from both ''in vitro'' and ''in vivo'' sources, and increase Antibiotics, antibiotic effectiveness against them.


Inhibitors

Many compounds are known that can act to inhibit the action of a glycoside hydrolase. Nitrogen-containing, 'sugar-shaped' heterocycles have been natural product, 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. Inhibitors that are in clinical use include the anti-diabetic drugs acarbose and miglitol, and the antiviral drugs oseltamivir and zanamivir. Some proteins have been found to act as glycoside hydrolase inhibitors.


See also

* Mucopolysaccharidoses * Glucosidase * Lysozyme * Glycosyltransferase * List of glycoside hydrolase families * :ru:Image:CAZy clans.jpg, Clans of glycoside hydrolases * :ru:Image:GH classification.jpg, Hierarchical classification of the TIM-barrel type glycoside hydrolases


References


External links


Cazypedia, an online encyclopedia of the "CAZymes," the carbohydrate-active enzymes and binding proteins involved in the synthesis and degradation of complex carbohydratesCarbohydrate-Active enZYmes DatabaseExPASy classification
* {{Authority control Carbohydrates Carbohydrate chemistry EC 3.2.1 Glycobiology