The conformational free energy landscape of β-D-glucopyranose. Implications for substrate preactivation in β-glucoside hydrolases

Xevi Biarnés, Albert Ardèvol, Antoni Planas, Carme Rovira, Alessandro Laio, Michele Parrinello

Research output: Indexed journal article Articlepeer-review

193 Citations (Scopus)

Abstract

Using ab initio metadynamics we have computed the conformational free energy landscape of β-D-glucopyranose as a function of the puckering coordinates. We show that the correspondence between the free energy and the Stoddard's pseudorotational itinerary for the system is rather poor. The number of free energy minima (9) is smaller than the number of ideal structures (13). Moreover, only six minima correspond to a canonical conformation. The structural features, the electronic properties, and the relative stability of the predicted conformers permit the rationalization of the occurrence of distorted sugar conformations in all the available X-ray structures of β-glucoside hydrolase Michaelis complexes. We show that these enzymes recognize the most stable distorted conformers of the isolated substrate and at the same time the ones better prepared for catalysis in terms of bond elongation/shrinking and charge distribution. This suggests that the factors governing the distortions present in these complexes are largely dictated by the intrinsic properties of a single glucose unit.

Original languageEnglish
Pages (from-to)10686-10693
Number of pages8
JournalJournal of the American Chemical Society
Volume129
Issue number35
DOIs
Publication statusPublished - 5 Sept 2007

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