Glycosidases: Functions, Families and Folds

The classification of glycosidases into families and clans on the basis of amino acid sequence has provided a foundation for the analysis of the structures and mechanisms of these important enzymes. This confluence of bioinformatic, structural and mechanistic studies has greatly advanced glycosidase engineering and the development of specific inhibitors.

Keywords: glycosidase; carbohydrate; glycoconjugate; enzyme; hydrolysis

Figure 1. Glycosidase folds: (a) (/)8 barrel; (b) jelly roll; (c) 5-fold propeller; (d) 6-fold propeller; (e) 7-fold propeller; (f) (/)6 barrel; (g) (/)7 barrel; (h) right-handed -helix; (i) dehydrogenase-like fold; and (j) lysozyme-like fold.
Figure 2. Glycosidase active site topologies: (a) pocket; (b) cleft; (c) tunnel. The position of the catalytic residues is shown in red.
Figure 3. Mechanisms of glycoside hydrolysis by glycosidases (R1=sugar, R2=H), transglycosylases (R1 and R2=sugars) and glycosidase-like phosphorylases (R1=sugar, R2=PO32–): (a) inverting -glycosidase; (b) inverting -glycosidase; (c) retaining -glycosidase; (d) retaining -glycosidase; (e) retaining N-acetyl -hexosaminidase; (f) Family 4 NAD+-dependent hydrolysis (X=PO32– or H); (g) Family 31 -glycan lyase.
Figure 4. Mechanisms of glycoside formation by engineered glycosidases: (a) glycosynthase; (b) thioglycoligase; (c) thioglycosynthase.
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 Further Reading
    Bourne Y and Henrissat B (2001) Glycoside hydrolases and glycosyltransferases: families and functional modules. Current Opinion in Structural Biology 11: 593–600.
    Davies GJ, Ducros VMA, Varrot A and Zechel DL (2003) Mapping the conformational itinerary of -glycosidases by X-ray crystallography. Biochemical Society Transactions 31: 523–527.
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    Mosi RM and Withers SG (2002) Trapping of -glycosidase intermediates. Methods in Enzymology 354: 64–84.
    Vocadlo DJ, Davies GJ, Laine R and Withers SG (2001) Catalysis by hen egg-white lysozyme proceeds via a covalent intermediate. Nature 412: 835–838.
    Zechel DL and Withers SG (2001) Dissection of nucleophilic and acid-base catalysis in glycosidases. Current Opinion in Chemical Biology 5: 643–649.
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Hancock, Susan M, and Withers, Stephen G(Sep 2007) Glycosidases: Functions, Families and Folds. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020548]