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(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.

N‐Benzyl Substitution of Polyhydroxypyrrolidines: The Way to Selective Inhibitors of Golgi α‐Mannosidase II

“…[46b] Metal atoms in enzymes represent a challenge for QM description. [47] The approach regarding the zinc atom in dGMII was described earlier. [13]…”

“…The hybrid operator projection (HOP) technique was adopted in the generation of fragments for the covalently bound amino acids . Metal atoms in enzymes represented a challenge for QM description . The approach regarding the zinc atom in dGMII was described earlier …”

Recent developments in symmetry‐adapted perturbation theory

“…266 Kłos et al, motivated by the buffer-gas cooling and magnetic trapping experiments, examined the SAPT(UKS) decomposition of the interaction energy between the helium atom and the ground, 6 Σ + state of the CrH molecule, making comparisons to a somewhat similar He-MnH( 7 Σ + ) complex. 267 Sladek and Tvaroška 268 compared, at the SAPT0 and SAPT(DFT) levels, the interactions between the closed-shell (Mg 2+ , Zn 2+ ) and open-shell (Mn 2+ ) cations and several ligands representing the active site of a metalloenzyme to investigate the influence of the metal ion on the enzyme's catalytic activity. Malenov and Zari c studied stacking interactions involving chelated complexes of Ni 2+ , Zn 2+ , and Cu 2+ , using closed-shell configurations for systems involving the first two ions but open-shell SAPT0 for the copper complexes.…”

UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase from the snail Biomphalaria glabrata – structural reflections

“…The strong interactions of Cu 2+ might cause a strong binding in the active site, disabling UDP to leave after the reaction and resulting in an inhibition of the enzyme. A computational study of manganese-dependent glycosyltransferases has shown that the interaction energies of Mn 2+ and Mg 2+ with the active site motifs of glycosyltransferases are similar [30,31]. However, Mn 2+ is more prone to replacement of the first solvation shell by the active site ligands than Mg 2+ .…”