7FE2

Crystal structure of the mutant E494Q of GH92 alpha-1,2-mannosidase from Enterococcus faecalis ATCC 10100 in complex with alpha-1,2-mannobiose

Summary for 7FE2

• Entry DOI: 10.2210/pdb7fe2/pdb
• Descriptor: Alpha-1,2-mannosidase, alpha-D-mannopyranose-(1-2)-beta-D-mannopyranose, CALCIUM ION, ... (7 entities in total)
• Functional Keywords: glycoside hydrolase, gh92, inhibitor, carbohydrate, n-glycan, hydrolase
• Biological source: Enterococcus faecalis ATCC 10100 (Streptococcus faecalis)
• Total number of polymer chains: 4
• Total formula weight: 334285.63

Authors

Miyazaki, T.,Alonso-Gil, S. (deposition date: 2021-07-19, release date: 2022-02-02, Last modification date: 2023-11-29)

Primary citation

Alonso-Gil, S.,Parkan, K.,Kaminsky, J.,Pohl, R.,Miyazaki, T.
Unlocking the Hydrolytic Mechanism of GH92 alpha-1,2-Mannosidases: Computation Inspires the use of C-Glycosides as Michaelis Complex Mimics.
Chemistry, 28:e202200148-e202200148, 2022

PubMed Abstract: 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 S →B → S and S → H → C . 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 C → H / S → S 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 E →B / S → S 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.

PubMed: 35049087
DOI: 10.1002/chem.202200148

Experimental method

X-RAY DIFFRACTION (1.75 Å)