Crystal structure of the retaining galactosyltransferase LgtC from Neisseria meningitidis in complex with donor and acceptor sugar analogs

Many bacterial pathogens express lipooligosaccharides that mimic human cell surface glycoconjugates, enabling them to attach to host receptors and to evade the immune response. In Neisseria meningitidis, the galactosyltransfe rase LgtC catalyzes a key step in the biosynthesis of lipooligosaccharide s tructure by transferring alpha -D-galactose from UDP-galactose to a termina l lactose. The product retains the configuration of the donor sugar glycosi dic bond; LgtC is thus a retaining glycosyltranferase, We report the 2 Angs trom crystal structures of the complex of LgtC with manganese and UDP 2-deo xy-2-fluoro-galactose (a donor sugar analog) in the presence and absence of the acceptor sugar analog 4'-deoxylactose. The structures, together with r esults from site-directed mutagenesis and kinetic analysis, give valuable i nsights into the unique catalytic mechanism and, as the first structure of a glycosyltransferase in complex with both the donor and acceptor sugars, p rovide a starting point for inhibitor design.