A new mechanism of nature to break down carbohydrates
One of the basic processes of nature is the decomposition of organic matter, which requires the degradation of complex carbohydrate structures. To do so, it is necessary to break the long chains of sugar molecules made up of smaller - ʻmonosaccharideʼ - units in order to transform them into short chains.
One of the basic processes of nature is the decomposition of organic matter, which requires the degradation of complex carbohydrate structures. To do so, it is necessary to break the long chains of sugar molecules made up of smaller - ʻmonosaccharideʼ - units in order to transform them into short chains.
The above process is performed by glycosidases, a superfamily of enzymes with relevant applications in biotechnology and biomedicine. Glycosidases can be found in all life forms and are part of the machinery by which cells acquire their nutrients.
In order to carry out these decomposition processes, only two catalytic mechanisms were known so far to help the acceleration of the corresponding chemical reactions. Recently, an international team of researchers discovered a third mechanism of nature, which goes through the formation of an epoxide chemical group, unprecedented in glycosidase catalysis. The team found this mechanism in a specific type of glycosidases: endo-α-mannosidases, necessary to modify the sugars linked to our proteins, as you can see in this animation:
According to Carme Rovira, ICREA Research Professor at the Department of Inorganic and Organic Chemistry, member of the Institute of Theoretical and Computational Chemistry of the University of Barcelona (IQTCUB) and one of the researchers that led the study, “this is the discovery of a new way of nature to break sugar chains through enzymes”.
The study has been published in the journal ACS Central Science, and carried out by the team led by Carme Rovira, as part of a collaborative effort involving four international groups from the United Kingdom, Australia, France and Canada. Other groups from the CIC Biogune center (Bilbao) have taken part in the study as well. The UB team has been in charge of modelling the enzyme mechanism of action using multiscale computational chemistry methods and supercomputers of thes Barcelona Supercomputing Center (BSC). “Learning the strategies of nature enables us to copy these to develop new enzymes with industrial applications”, notes Lluís Raich, former PhD student of the group led by Rovira, and one of the first authors of the study.
The journal also publishes a commentary article in which Professor David Vocadlo, expert in this field, from Simon Fraser University (Canada), notes that the study “provides the first convincing data to prove this particular mechanism from glycosidases, which will probably be used by other enzymes yet to be discovered”.
Further information
Read the piece of news available in the University of Melbourne.
Article reference:
Lukasz, F. Sobala et al. "An epoxide intermediate in glycosidase catalysis". ACS Central Science, 2020, 6, 5, 760-770. Doi: https://doi.org/10.1021/acscentsci.0c00111
David J. Vocadlo "A shut-and-open case: an epoxide intermediate spotted in the reaction coordinate of a family of glycoside hydrolases". ACS Central Science, 2020, 6, 5, 619-621. Doi: 10.1021/acscentsci.0c00482