Mechanism retaining glycosidase

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. 

Application of ALPH to retaining glycosidases, then, presents the theory with insuperable difficulties if conventional mechanisms for these enzymes... 

Heightman, T D, Vasella, A T, Recent insights into inhibition, stmcture, and mechanism of configuration-retaining glycosidases, Angew. Chem., Int. Ed., 38, 750-770, 1999. 

Figure 5.32 Canonical mechanism for a retaining glycosidase or transglycosylase Whether the substrates are pyranosidases or furanosidases, whether the leaving group is axial or equatorial and whether the protonation trajectory is syn or anti depend on the enzyme. If R = R, then the principle of microscopic reversibility requires transition states 1 and 2 to be identical. More generally, the group which acts as a general acid in the first step must act as a general base in the second.

Scheme 2 General mechanism utilized by retaining glycosidases.

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