Neisserial pathogens exhibit heterogeneity in their lipooligosaccharide (LOS) structure, which enables them to escape the innate immune response and enhances disease progression (Griffiss et al., 1988). Addition of phosphoethanolamine (PEA) moieties to different locations on the LOS contributes to their heterogeneity.  This addition is catalyzed by a class of enzymes called PEA transferases. Neisserial pathogens have 3 different PEA transferases that catalyze the addition of PEA from phosphatidylethanolamine, to specific sites on the LOS.  In order to understand the mechanism of catalysis and substrate specificity by PEA transferases structural studies of these enzymes by X-ray crystallography are being undertaken.

Lpt3 catalyzes the addition of PEA to the C3 position of the distal heptose of the LOS (O'Connor et al., 2006). Lpt3 shares sequence identity with other neisserial phosphoethanolamine transferases using the same substrates but exhibiting different linkage specificities (Kahler et al., 2005). Gene knock-out experiments have shown that the function of Lpt3 is not replaced by other PEA transferases found in the neisserial pathogens (Griffiss et al., 1988). Lpt3 has been predicted to be an integral membrane protein consisting of a transmembrane domain and a periplasmic domain (Kahler et al., 2005). The enzyme has been expressed in a recombinant E. coli expression system, purified to homogeneity and crystallized for X-ray diffraction studies. Our progress towards the structure will be presented.