Unlocking the Hydrolytic Mechanism of GH92 α-1,2-Mannosidases: Computation Inspires the use of C-Glycosides as Michaelis Complex Mimics

0553763 - ÚOCHB 2023 RIV DE eng J - Článek v odborném periodiku
Alonso-Gil, S. - Parkan, K. - Kaminský, Jakub - Pohl, Radek - Miyazaki, T.
Unlocking the Hydrolytic Mechanism of GH92 α-1,2-Mannosidases: Computation Inspires the use of C-Glycosides as Michaelis Complex Mimics.
Chemistry - A European Journal. Roč. 28, č. 14 (2022), č. článku e202200148. ISSN 0947-6539. E-ISSN 1521-3765
Grant CEP: GA MŠMT LTAUSA18085
Institucionální podpora: RVO:61388963
Klíčová slova: carbohydrates * conformations * enzymology * inhibitors * quantum mechanics
Obor OECD: Physical chemistry
Impakt faktor: 4.3, rok: 2022
Způsob publikování: Open access
https://doi.org/10.1002/chem.202200148

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-O(2)-> B-2,B-5> S-1(5) and S-3(1)-> H-3(4)-> C-1(4). 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-4(1)-> H-4(5)/S-1(5)-> S-1(5) 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-5> B-2,B-5/S-1(5)-> S-1(5) 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.
Trvalý link: http://hdl.handle.net/11104/0328491


Vědecká data: RCSB PDB, RCSB PDB