First-Principles Interaction Analysis Assessment of the Manganese Cation in the Catalytic Activity of Glycosyltransferases.

The energetic effect of water substitution reactions in hexacoordinated [Mn(HO)L] complexes with L = methanol, formic acid, formamide, formate, imidazole, and diphosphate is quantitatively analyzed at the MP2/triple-ζ level of theory. Subsequently, the state-of-the-art open shell symmetry-adapted perturbation theory (SAPT) analysis of the interaction energies of Mn···ligand dimers with selected O-, S-, and N-binding ligands is presented and compared to similar interactions of Mg and Zn ions. We find that the induction energies in the dimers with manganese are almost twice as large as in dimers with magnesium. The total interaction energies rise in the order Mn < Mg < Zn. The calculations of the Mn → Mg replacement reaction suggest that metal-dependent glycosyltransferases influence the binding preference of Mn over Mg by inserting amino acids that coordinate the metal via nitrogen or sulfur into their active site.