When talking about glycosidases – the main enzymes responsible for degrading carbohydrates in Nature – one often refers to the “catalytic itinerary”. This is the set of chemical and structural modifications that a certain substrate (typically a carbohydrate molecule) undergoes while it is being cleaved by the enzyme (broken into pieces). One of the main features of the catalytic itinerary is the “shape” or conformation of the substrate, i.e. the so-called “conformational catalytic itinerary”.
Until now, it was assumed that the conformational catalytic itinerary was unique for each glycosidase enzyme (and even for all members of the same family of enzymes). By means of a multidisciplinary work involving protein crystallography and quantum mechanics/molecular mechanics simulations, we demonstrate that this paradigm breaks for certain enzymes acting on hemicellulose (a polysaccharide of plant cell walls). Exo-oligoxylanases from the pathogen Xanthomonas citri – classified in the family 43 of glycosidases – can cleave the terminal end of plant carbohydrates via two alternative catalytic itineraries.
These results will serve to find ways to redesign glycosidase active sites (the region of the enzyme that binds and converts the substrate in a product), as well as designing inhibitor molecules that suppress the enzyme activity to fight the pathogen.
The work is a collaboration between researchers from the Brazilian Biorenewables National Laboratory (Campinas, Brazil), led by Mario Murakami, and the group of Quantum Simulation of biological Processes of the Department of Chemistry of the University of Barcelona, led by Carme Rovira.
