Structural characterization of a flavonoid glycosyltransferase from Withania somnifera

Medicinal plants are extensively utilized in traditional and herbal medicines, both in India and around the world due to thepresence of diverse low molecular weight natural products such as flavonoids, alkaloids, terpenoids and sterols. Flavonoids whichhave health benefits for humans are the large class of phenylpropanoid-derived secondary metabolites and are mostly glycosylatedby UDP-glycosyltransferases (UGTs). Although large numbers of different UGTs are known from higher plants, very few proteinstructures have been reported till now. In the present study, the three-dimensional model of flavonoid specific glycosyltransferases(WsFGT) from Withania somnifera was constructed based on the crystal structure of plant UGTs. The resulted model was assessedby various tools and the final refined model revealed GT-B type fold. Further, to understand the sugar donors and acceptorsinteractions with the active site of WsFGT, docking studies were performed. The amino acids from conserved PSPG box wereinteracted with sugar donor while His18, Asp110, Trp352 and Asn353 were important for catalytic function. This structural anddocking information will be useful to understand the glycosylation mechanism of flavonoid glucosides.

Abbreviations

DOPE - Discrete Optimized Potential Energy, PDB - Protein Data Bank, PSPG - Plant Secondary Product Glycosyltransferase, RMSD - Root Mean Squared Deviation, UDP - Uridine diphosphate, UGT - UDP-glycosyltransferases.