Unlocking the hydrolytic mechanism of GH92 α-1,2-mannosidases: computation inspires using C-glycosides as Michaelis complex mimics
semanticscholar(2021)
摘要
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 OS2 B2,5 1S5 and 3S 3H4 1C4. 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 4C1 4H5/1S5 1S5 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 B2,5/1S5 1S5 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.
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