Seminar

Molecular mechanisms of enzymatic glycosyl transfer. Insight from QM/MM metadynamics

Carme Rovira, PhD

Glycosyltransferases (GTs) are highly specific enzymes that catalyze the formation of glycosidic bonds in carbohydrates. In contrast to the well-characterized double-displacement mechanism used by retaining glycoside hydrolases (ret-GHs) to catalyze the cleavage of glycosidic bonds, the mechanisms of retaining GTs have been debated for years, although there is now increasing evidence that many ret-GTs operate via the (once considered unusual) SNi-like reaction, in which leaving group departure and nucleophile approach occur on the same ‘front’ face. Here I will summarize our work on the prediction of catalytic mechanisms of ret-GTs and engineered ret-GHs by means of quantum mechanics/molecular mechanics (QM/MM) metadynamics approaches, showing that the SNi-like reaction is more widespread than what was early assumed. Dr. Rovira is an ICREA Research Professor at the Department of Chemistry of the University of Barcelona. She did part of her PhD research in USA (North Carolina State University and Southern Illinois University) and obtained her PhD degree in Chemistry from the UB in 1995, working with J. J. Novoa. Afterwards, she spent three years (1996-1998) as postdoctoral fellow at the Max-Planck-Institute für Festkörperforschung (Stuttgart, Germany), working with M. Parrinello. In 2002 she obtained a Ramón y Cajal position and moved to the Parc Científic de Barcelona. She received an award from the Generalitat de Catalunya ("Distinció de la Generalitat per la promoció de la recerca universitaria", young scientist category) in 2003 and in 2007 she was appointed ICREA Research Professor. She moved to the Department of Chemistry of the UB in 2012. Dr. Rovira is the author of about 120 publications in peer-reviewed journals, mainly in the fields of Theoretical Chemistry and Computational Biology. The research at Dr. Rovira´s group is focused on the computer simulation of biological processes at atomic-electronic detail, i.e. using computers to understand how biomolecules work. Her goal is to simulate the molecular mechanisms underlying ligand-protein interactions and enzymatic reactions to help in the design of more efficient enzymes and inhibitors. In the last few years, her research has been focused on hemeproteins (peroxidases and catalases) and carbohydrate-active enzymes.