Retaining glycosidases

Glycosyl transferases and O-glycosidases modify glycoproteins and are important for polysaccharide catabolism. Inhibitors of these enzymes are potential drugs in the treatment of cancer, viral infection and diabetes. There are two mechanistic classes of glycosidases, retaining and inverting." ... 

Inhibition of configuration-retaining glycosidases by lactones, piperidines, and tetrazoles 99AG(E)750. 

T. D. Heightman, A T. Vasella, Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases , Angew. Chem. Int. Ed. 1999, 38,750-770. 

A Hydrolysis mechanism of retaining glycosidase (R = saccharide or alcohol) - double inversion at the anomeric centre. 

Scheme 2 Hydrolysis mechanisms of retaining (A) and inverting (B) glycosidase and P-A-acetylhexosaminidase, which uses a modified retaining mechanism (C).

A very important group of secondary hydroxyl modifications represent fluoroglycosides.104 When they interact with a retaining glycosidase, the highly electronegative fluorine on the carbohydrate ring causes the destabilization of both transition states and the reaction proceeds at a... 

Thioglycosynthase a double mutant of a retaining glycosidase, in which both the catalytic nucleophile and the catalytic acid-base residue at the active site have been substituted by non-nucleophilic residues. It... 

Figure 1. Reaction mechanism of retaining b-glycosidases. R aglycon group. R = H, hydrolysis. R = alcohol, transglycosylation.

Figure 2. Azide rescue of an acid/base catalyst (A) and a nucleophile (B) mutant of a retaining b-glycosidase. R aglycon group.

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