Structural and mechanistic themes in glycoconjugate biosynthesis at membrane interfaces.

Peripheral and integral membrane proteins feature in stepwise assembly of complex glycans and glycoconjugates. Catalysis on membrane-bound substrates features challenges with substrate solubility and active-site accessibility. However, advantages in enzyme and substrate orientation and control of lateral membrane diffusion provide order to the multistep processes. Recent glycosyltransferase (GT) studies show that substrate diversity is met by the selection of folds which do not converge upon a common mechanism. Examples of polyprenol phosphate phosphoglycosyl transferases (PGTs) highlight that divergent fold families catalyze the same reaction with different mechanisms. Lipid A biosynthesis enzymes illustrate that variations on the robust Rossmann fold allow substrate diversity. Improved understanding of GT and PGT structure and function holds promise for better function prediction and improvement of therapeutic inhibitory ligands.