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Crystal structure of the mutant E494Q of GH92 alpha-1,2-mannosidase from Enterococcus faecalis ATCC 10100 in complex with alpha-1,2-mannobioseCrystal structure of the mutant E494Q of GH92 alpha-1,2-mannosidase from Enterococcus faecalis ATCC 10100 in complex with alpha-1,2-mannobiose
Structural highlights
FunctionPublication Abstract from PubMedThe 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 3S1 --> 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. Unlocking the hydrolytic mechanism of GH92 alpha-1,2-mannosidases: computation inspires using C-glycosides as Michaelis complex mimics.,Alonso-Gil S, Parkan K, Kaminsky J, Pohl R, Miyazaki T Chemistry. 2022 Jan 20. doi: 10.1002/chem.202200148. PMID:35049087[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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