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

Producción científica: Artículo en revista indizadaArtículorevisión exhaustiva

43 Citas (Scopus)

Resumen

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 originalInglés
Páginas (desde-hasta)16058-16065
Número de páginas8
PublicaciónJournal of the American Chemical Society
Volumen132
N.º45
DOI
EstadoPublicada - 17 nov 2010

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Profundice en los temas de investigación 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'. En conjunto forman una huella única.

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