The conformational free-energy landscape of beta-D-mannopyranose: evidence for a S-1(5) -> B-2,B-5 -> S-O(2) catalytic itinerary in beta-mannosidases

Albert Ardèvol, Xevi Biarnés, Antoni Planas, Carme Rovira

Producció científica: Article en revista indexadaArticleAvaluat per experts

43 Cites (Scopus)

Resum

The mechanism of glycosidic bond cleavage by glycosidases involves substrate ring distortions in the Michaelis complex that favor catalysis. Retaining β-mannosidases bind the substrate in a 1S5 conformation, and recent experiments have proposed an unusual substrate conformational pathway (1S5 → B2,5OS2) for the hydrolysis reaction. By means of Car-Parrinello metadynamics simulations, we have obtained the conformational free-energy surface (FES) of a β-d-mannopyranose molecule associated with the ideal Stoddart conformational diagram. We have found that 1S 5 is among the most stable conformers and simultaneously is the most preactivated conformation in terms of elongation/shortening of the C1-O1/C1-O5 bonds, C1-O1 orientation, and charge development at the anomeric carbon. Analysis of the computed FES gives support to the proposed 1S 5 → B2,5OS2 catalytic itinerary, showing that the degree of preactivation of the substrate in glycoside hydrolases (GHs) is related to the properties of an isolated sugar ring. We introduce a simple preactivation index integrating several structural, electronic, and energetic properties that can be used to predict the conformation of the substrate in the Michaelis complex of any GH.

Idioma originalAnglès
Pàgines (de-a)16058-16065
Nombre de pàgines8
RevistaJournal of the American Chemical Society
Volum132
Número45
DOIs
Estat de la publicacióPublicada - 17 de nov. 2010

Fingerprint

Navegar pels temes de recerca de 'The conformational free-energy landscape of beta-D-mannopyranose: evidence for a S-1(5) -> B-2,B-5 -> S-O(2) catalytic itinerary in beta-mannosidases'. Junts formen un fingerprint únic.

Com citar-ho