2024/12/10

New study uncovers the molecular mechanisms behind glycan cleavage

Glycan hydrolysis, driven by glycosyl hydrolases, is a vital biochemical process that breaks down glycosidic bonds and plays a key role in various biological functions.

The international study, published in the Journal of the American Chemical Society (JACS), has provided a detailed characterization of the three-dimensional structures of glycosyl cations, essential intermediates in glycan formation and cleavage.

An international team of researchers has made a significant breakthrough in the study of glycans, essential molecules for life. Their work, published in the prestigious Journal of the American Chemical Society (JACS), reveals the detailed three-dimensional structures of glycosyl cations—short-lived intermediates that play a key role in the biochemical processes of glycan formation and cleavage. These processes are vital for many biological functions, including those involved in immunity, cell signaling, and metabolism.

The study, titled “Glycosylium Ions in Superacid Mimic the Transition State of Enzyme Reactions”, provides a clearer understanding of how glycosyl cations are formed during enzymatic reactions. Using a combination of advanced chemical synthesis, nuclear magnetic resonance (NMR) spectroscopy, and computational studies, the researchers were able to observe these fleeting structures in super acidic conditions. They found that these glycosyl cations resemble the transition states that occur in the active sites of enzymes during glycan processing.

“This investigation highlights two key aspects of disruptive research: the importance of multidisciplinarity, combining different experimental techniques with computational tools, to address essential scientific questions, as well as the value of international collaboration, crossing borders and integrating teams with distinct expertise in a synergic manner” explain Dr. Ana Ardá and Prof. Jesús Jiménez-Barbero.

The success of the study was made possible through the collaboration of researchers from the University of Poitiers, the University of Barcelona, and CIC bioGUNE – member of BRTA -, including Dr. Ana Ardá and Prof. Jesús Jiménez-Barbero, Ikerbasque researchers leading the Chemical Glycobiology group at the center. Their combined efforts with Dr. Carme Rovira’s computational group at the University of Barcelona integrated both experimental and theoretical approaches, providing a comprehensive understanding of these highly reactive molecules.

The findings not only enhance our understanding of glycans in living organisms but also have potential applications in medicine. The research could pave the way for new drug designs, such as inhibitors for enzymes that interact with glycans, offering new approaches to understand the molecular mechanisms behind diseases like cancer or viral infections in order to combat them.

This work exemplifies the power of interdisciplinary collaboration and the potential of new experimental techniques in scientific research. It also highlights the importance of CIC bioGUNE as a key player in the study of chemical glycobiology.

Reference: Mathilde Armand, Alba Nin-Hill, Ana Ardá, Emanuela Berrino, Jérôme Désiré, Agnès Martin-Mingot, Bastien Michelet, Jesús Jiménez-Barbero,* Yves Blériot,* Carme Rovira,* Sébastien Thibaudeau*. Glycosylium Ions in Superacid Mimic the Transition State of Enzyme Reactions. J. Am. Chem. Soc. DOI: 10.1021/jacs.4c11677.

About CIC bioGUNE
The Centre for Cooperative Research in Biosciences (CIC bioGUNE), member of the Basque Research & Technology Alliance (BRTA), located in the Bizkaia Technology Park, is a biomedical research organisation conducting cutting-edge research at the interface between structural, molecular and cell biology, with a particular focus on generating knowledge on the molecular bases of disease, for use in the development of new diagnostic methods and advanced therapies.

About Ikerbasque
Ikerbasque - Basque Foundation for Science - is the result of an initiative of the Department of Education of the Basque Government that aims to reinforce the commitment to scientific research by attracting, recovering and consolidating excellent researchers from all over the world. Currently, it is a consolidated organization that has 290 researchers/s, who develop their work in all fields of knowledge.

About BRTA
BRTA is an alliance of 4 collaborative research centres (CIC bioGUNE, CIC nanoGUNE, CIC biomaGUNE y CIC energiGUNE) and 13 technology centres (Azterlan, Azti, Ceit, Cidetec, Gaiker, Ideko, Ikerlan, Leartiker, Lortek, Neiker, Tecnalia, Tekniker y Vicomtech) with the main objective of developing advanced technological solutions for the Basque corporate fabric.

With the support of the Basque Government, the SPRI Group and the Provincial Councils of the three territories, the alliance seeks to promote collaboration between the research centres, strengthen the conditions to generate and transfer knowledge to companies, contributing to their competitiveness and outspreading the Basque scientific-technological capacity abroad.

BRTA has a workforce of 3,500 professionals, executes 22% of the Basque Country's R&D investment, registers an annual turnover of more than 300 million euros and generates 100 European and international patents per year.

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