Crystal structure of a UDP-glucose-specific glycosyltransferase from a Mycobacterium species

Glycosyltransferases (GTs) are a large and ubiquitous family of enzymes that specifically transfer sugar moieties to a range of substrates. Mycobacterium tuberculosis contains a large number of GTs, many of which are implicated in cell wall synthesis, yet the majority of these GTs remain poorly characterized. Here, we report the high-resolution crystal structures of an essential GT (MAP2569c) from Mycobacterium avium subsp. paratuberculosis (a close homologue of Rv1208 from M. tuberculosis) in its apo- and ligand-bound forms. The structure adopted the GT-A fold and possessed the characteristic D-x-D motif that coordinated a Mn2+ ion. Atypical of most GTs characterised to date, MAP2569c exhibited specificity towards the donor substrate, UDP-glucose. The structure of this ligated complex revealed an induced-fit binding mechanism and provided a basis for this unique specificity. Collectively, the structural features suggested MAP2569c adopted a retaining enzymatic mechanism, which has implications for the classification of other GTs in this large superfamily.