The Molecular Mechanism of Enzymatic Glycosyl Transfer with Retention of Configuration: Evidence for a Short-Lived Oxocarbenium-Like Species

Authors

  • Albert Ardèvol,

    1. Computer Simulation and Modeling Laboratory (CoSMoLAB), Parc Científic de Barcelona, Baldiri Reixac 10–12, 08028 Barcelona (Spain)
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  • Prof. Carme Rovira

    Corresponding author
    1. Computer Simulation and Modeling Laboratory (CoSMoLAB), Parc Científic de Barcelona, Baldiri Reixac 10–12, 08028 Barcelona (Spain)
    2. Institució Catalana de Recerca i Estudis Avançats (ICREA), Passeig Lluís Companys 23, 08020 Barcelona (Spain)
    • Computer Simulation and Modeling Laboratory (CoSMoLAB), Parc Científic de Barcelona, Baldiri Reixac 10–12, 08028 Barcelona (Spain)
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  • We thank Prof. A. Planas, Prof. B. G. Davis, and Dr. S. S. Lee for enlightening discussions on the mechanisms of GTs. This work was funded by the MICINN (FIS2008-03845) and GENCAT (2009SGR-1309). A.A. thanks MEC for a FPU studentship. We acknowledge the computer support, technical expertise, and assistance provided by the Barcelona Supercomputing Center-Centro Nacional de Supercomputación (BSC-CNS).

Abstract

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A quantum leap: By means of quantum mechanics/molecular mechanics metadynamics simulations, a front-face SNi-type reaction for glycosyl transfer with retention of the anomeric configuration is shown to be feasible. A short-lived oxocarbenium-like species (see picture; O red, P gold, N blue, C black) is identified and provides the complete itinerary of this long sought after molecular mechanism.

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