2020/04/23

CIC bioGUNE researchers have participated in a collective international effort to unravel a new mechanism in biological catalysis.

The existence of a new 1,2-anhydro sugar intermediate in glycoside hydrolysis has been deduced by a combination of methodologies, including organic synthesis, QM/MM calculations, KIE measurements, mass spectrometry, NMR spectroscopy and X-Ray crystallography. Strikingly, the novel conformational pathway that leads to the product is completely distinct from that used by all other previously characterized mannosidase enzymes. Moreover, the existence of this mechanism is broadly equivalent to that proposed for 1,2-anhydro sugars, which have long been implicated as intermediates in the base-promoted hydrolysis of trans-1,2-glycosides.

This breakthrough, just published in ACS Central Science is the result of a long collaboration of the Chemical Glycobiology and Precision Medicine and Metabolism labs at CIC bioGUNE with the labs of S. J. Williams (University of Melbourne), G. J. Davies (University of York), C. Rovira (University of Barcelona), M. Sollogoub (Sorbonne University, Paris), and A. J. Bennet (Simon Fraser University, Vancouver).