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

Abstract

The energetic effect of water substitution reactions in hexacoordinated [Mn(H₂O)_6-nL^z_n]^2+nz 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 Mn²⁺···ligand dimers with selected O-, S-, and N-binding ligands is presented and compared to similar interactions of Mg²⁺ and Zn²⁺ 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 Mn²⁺ < Mg²⁺ < Zn²⁺. The calculations of the Mn²⁺ → Mg²⁺ replacement reaction suggest that metal-dependent glycosyltransferases influence the binding preference of Mn²⁺ over Mg²⁺ by inserting amino acids that coordinate the metal via nitrogen or sulfur into their active site.