New enzyme catalyzing the formation of glyc
Carbohydrate chains play physiologically relevant roles. For example, many biologically important proteins and lipids inside our body have carbohydrate chains attached to them. These “sweet” chains even play a key role in altering the functions of organic molecules such as the aromatic compounds to which they are commonly attached. It is a known fact that these carbohydrate structures can alter the functions of compounds related to them. The biological synthesis of these chains takes place via biochemical reactions which are catalyzed by enzymes such as glycosyltransferases. However, the commercial production of carbohydrate chains poses several technical challenges.
A group of collaborating researchers from Tokyo University of Science and Niigata University have now been able to determine the structure and activity of a new enzyme exhibiting glycosyltransferase activity. The results of this study were posted online on January 19, 2022 and published in Volume 298, Number 3 of the Journal of Biological Chemistry.
Dr. Masahiro Nakajima, associate professor at Tokyo University of Science and lead author of the study, explains: “The structures and functions of enzymes that synthesize and break down carbohydrate chains have diversified considerably through molecular evolution. To date, various types of carbohydrate-related enzymes have been found and added to the Carbohydrate-Active enZYmes or CAZy database. This database classifies these enzymes, called CAZymes, into families primarily based on their amino acid sequences and is growing. However, obtaining carbohydrates is often difficult due to their scarcity or inhomogeneity in nature, which limits the exploration of new enzymes..”
The β-1,2-glucan polysaccharide is a homopolymer comprising β-1,2-linked glucose units. This carbohydrate cannot be readily obtained in commercially viable quantities from natural resources using any of the known experimental techniques. Although β-1,2-glucans are implicated in bacterial infection, hypo-osmotic adaptation, and iron storage, their precise mechanism of action remains elusive; largely limited by their unavailability. This unavailability stems from the paucity of research on enzymes associated with β-1,2-glucan metabolism.
The enzyme endo-β-1,2-glucanase is involved in the metabolism of β-1,2-glucan. Using advanced techniques for structure determination and biochemical characterization, including mutagenesis and estimation of reaction rates, the research team identified the biochemical function of a novel enzyme associated with β-1 ,2-glucan.
Dr. Nakajima ponders, “We have discovered an enzyme that performs a new chemical reaction. Our new mechanism of action has paved the way for the synthesis of incredibly difficult to synthesize sugar chains. Although several glycans are involved in biologically important roles, there are many whose functions cannot be fully understood due to low reaction yields. We believe this discovery has expanded the possibilities for the successful development and use of sugar chains. »
The IALB_1185 (IaSGT) protein, encoded in the cluster of genes that codes for endo-β-1,2-glucanase homologs, is listed as a glycoside hydrolase family 35 (GH35) protein. However, contrary to expectations, the team noticed that IaSGT is actually a “glycosyltransferase” acting on β-1,2-glucosidic bonds. This was a novel catalytic activity demonstrated by the protein. While glycoside hydrolases catalyze the breaking or hydrolysis of glycosidic bonds, a chemical reaction that involves water, glycosyltransferases do the exact opposite: they catalyze the formation of these bonds. Based on these findings, the team proposes “β-1,2-glucooligosaccharide:D-glucoside β-D-glucosyltransferase” as a systematic name and “β-1,2-glucosyltransferase” as an accepted name for IALB_1185.
Dr. Hiroyuki Nakai, Associate Professor at Niigata University and senior collaborator on the study, comments, “Glycosyltransfer reactions are useful for the synthesis of oligosaccharides, but the glycosyltransferases of the glycoside hydrolase families share their reaction mechanisms with the glycoside hydrolases. Therefore, we need a complete understanding of their reaction mechanism to freely control the conversion between transferases and hydrolases. Our findings are important biochemical data for understanding CAZyme diversity and a fundamental structural basis for further investigation into the deep enigma of CAZyme reaction mechanisms.
The research community surely hopes that the newly discovered and functionally characterized enzyme will accelerate the synthesis of carbohydrate chains that play a key role in various biological processes. Sweet news indeed!
About Tokyo University of Science
Tokyo University of Science (TUS) is a well-known and respected university, and the largest private research university specializing in science in Japan, with four campuses in central Tokyo and its suburbs and in Hokkaido. Founded in 1881, the university has continuously contributed to the scientific development of Japan by instilling a love of science in researchers, technicians and educators.
With a mission to “create science and technology for the harmonious development of nature, human beings and society”, TUS has undertaken a wide range of research from basic science to applied science. TUS has taken a multidisciplinary approach to research and undertaken intensive studies in some of today’s most vital areas. TUS is a meritocracy where the best in science is recognized and nurtured. It is the only private university in Japan that has produced a Nobel laureate and the only private university in Asia to produce Nobel laureates within the field of natural sciences.
About Associate Professor Masahiro Nakajima of Tokyo University of Science
Dr. Masahiro Nakajima is an associate professor at Tokyo University of Science, where he primarily conducts research on carbohydrates and enzyme structures using techniques such as X-ray crystallography. His research group determines the mechanism action of enzymes that act on sugar chains with unique structures. The group also focuses on protein engineering, structural biology, enzyme-catalyzed mass synthesis of carbohydrate chains and aims to establish methods for protein design through comparative enzyme analysis. Dr. Nakajima has published over 35 articles in peer-reviewed journals and has one patent to his name.
Journal of Biological Chemistry
The title of the article
Characterization and structural analyzes of a new glycosyltransferase acting on β-1,2-glucosidic bonds
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Conflict of Interest Statement
The authors declare no conflict of interest directly related to the content of this article.
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