The conformational changes in a sugar moiety along the hydrolytic pathway are key to understand the mechanism of glycoside hydrolases (GHs) and to design new inhibitors. The two predominant itineraries for mannosidases go via O S2 →B2,5 →1 S5 and 3 S1 →3 H4 →1 C4 . For the CAZy family 92, the conformational itinerary was unknown. Published complexes of Bacteroides thetaiotaomicron GH92 catalyst with a S-glycoside and mannoimidazole indicate a 4 C1 →4 H5 /1 S5 →1 S5 mechanism. However, as observed with the GH125 family, S-glycosides may not act always as good mimics of GH's natural substrate. Here we present a cooperative study between computations and experiments where our results predict the E5 →B2,5 /1 S5 →1 S5 pathway for GH92 enzymes. Furthermore, we demonstrate the Michaelis complex mimicry of a new kind of C-disaccharides, whose biochemical applicability was still a chimera.

• Klíčová slova
• carbohydrates, conformations, enzymology, inhibitors, quantum mechanics,
• MeSH
• glykosidhydrolasy metabolismus   MeSH
• glykosidy * chemie   MeSH
• mannosidasy * chemie   MeSH
• molekulární konformace MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• C-glycoside MeSH Prohlížeč
• glykosidhydrolasy MeSH
• glykosidy * MeSH
• mannosidasy * MeSH