Molecular dynamics simulations of solvated UDP-glucose in interaction withMg2+ cations

Glycosyltransferases are key enzymes involved in biosynthesis of oligosacch arides. Nucleotide-sugars, the glycosyltransferase substrates, serve as act ivated donors of sugar residues during the enzymatic reaction Although very little is known about the catalytic mechanism of these enzymes, it appears that the catalytic activity in most glycosyltransferases is dependent upon the presence of a divalent cation, for example Mn2+ or Mg2+. It is not kno wn whether the ion is bound to the enzyme before its interaction with the s ubstrate, or if it binds the substrate before the enzymatic reaction to mod ify its conformation to fit better the active site of the enzyme. We have i nspected the latter possibility by running four 2-ns molecular dynamics tra jectories on fully solvated UDP-glucose in the presence of Mg2+ ions. Our r esults indicate that the divalent cation interacts strongly with the nucleo tide-sugar in solution, and that it can alter its conformational behavior. It is also shown that a conformation of the pyrophosphate moiety that resul ts in an eclipsed or almost eclipsed orientation of two of the oxygen atoms , and which is found in protein interacting with a nucleotide di- or tri-ph osphate X-ray data, is energetically favored. The results are also discusse d in light of existing NMR data, and are found to be in a good agreement wi th them.