Structural insights into branch-forming glycosyltransferases.
As if the chemical diversity of plant metabolites were not already vast enough, the repertoire of compounds can be considerably expanded even further by various modifications. One of the most common modifications is glycosylation, the adding of one or more sugar moieties to a metabolite. Plant metabolite glycosylation is catalyzed almost exclusively by glycosyltransferases, mainly by Uridine-diphosphate (UDP) dependent Glycosyltransferases (UGTs). But besides those UGTs, there are also sugar-sugar/branch-forming O-linked UGTs (SBGTs) that catalyze the transfer of a sugar from the UDP-sugar donor to an acceptor sugar moiety of a previously glycosylated metabolite substrate. Very little is known regarding structure-function aspects of SBGTs.
To better understand the structural basis for catalytic activity of these enzymes, IPB scientists together with Israeli colleagues have now modelled the 3D-structures of two plant SBGT enzymes: a rhamnosyl-transferase that catalyzes rhamnosylation of specific flavonoid-glucosides and a glycosyltransferase that glucosylates (+)-Sesaminol 2-O-β-D-glucoside. Based on their structural models and docking experiments, the researchers found a glutamate and a tryptophan residue that appear to interact with the sugar acceptor. These residues, they suggest, could be important for the recognition of the sugar moiety. With substitution mutants for these two residues in the rhamnosyl-transferase, the researchers were able to further corroborate their role in determining sugar-sugar/branch-forming GT specificity. Finally, a phylogenetic analysis of the UGT family in plants revealed the glutamate residue as a hallmark of SBGTs that is entirely absent from the corresponding position in primary UGTs.
Since modifications like glycosylation often influence solubility, toxicity, and many more important properties of a metabolite, insights on these processes can be helpful to tailor useful compounds with specific features.
Original publication:
Brandt W, Schulze E, Liberman-Aloni R, Bartelt R, Pienkny S, Carmeli-Weissberg M, Frydman A, Eyal Y (2021). Structural modeling of two plant UDP-dependent sugar-sugar glycosyltransferases reveals a conserved glutamic acid residue that is a hallmark for sugar acceptor recognition, Journal of Structural Biology, Volume 213, Issue 3, 107777, doi.org/10.1016/j.jsb.2021.107777
