Unlocking the Hydrolytic Mechanism of GH92 alpha-1,2-Mannosidases: Computation Inspires the use of C-Glycosides as Michaelis Complex Mimics
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22330%2F22%3A43924745" target="_blank" >RIV/60461373:22330/22:43924745 - isvavai.cz</a>
Výsledek na webu
<a href="https://doi.org/10.1002/chem.202200148" target="_blank" >https://doi.org/10.1002/chem.202200148</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/chem.202200148" target="_blank" >10.1002/chem.202200148</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Unlocking the Hydrolytic Mechanism of GH92 alpha-1,2-Mannosidases: Computation Inspires the use of C-Glycosides as Michaelis Complex Mimics
Popis výsledku v původním jazyce
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.
Název v anglickém jazyce
Unlocking the Hydrolytic Mechanism of GH92 alpha-1,2-Mannosidases: Computation Inspires the use of C-Glycosides as Michaelis Complex Mimics
Popis výsledku anglicky
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.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
10403 - Physical chemistry
Návaznosti výsledku
Projekt
—
Návaznosti
S - Specificky vyzkum na vysokych skolach
Ostatní
Rok uplatnění
2022
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Chemistry A European Journal
ISSN
0947-6539
e-ISSN
1521-3765
Svazek periodika
28
Číslo periodika v rámci svazku
14
Stát vydavatele periodika
DE - Spolková republika Německo
Počet stran výsledku
6
Strana od-do
nestrankovano
Kód UT WoS článku
000750616400001
EID výsledku v databázi Scopus
2-s2.0-85124159903