Protein-Assisted Formation and Stabilization of Catalytically Active Polyoxometalate Species

Abstract

The effect of the protein environment on the formation and stabilization of an elusive catalytically active polyoxometalate (POM) species, K₆ [Hf(α₂ -P₂ W₁₇ O₆₁ )] (1), is reported. In the co-crystal of hen egg-white lysozyme (HEWL) with 1, the catalytically active monomeric species is observed, originating from the dimeric 1:2 POM form, while it is intrinsically unstable under physiological pH conditions. The protein-assisted dissociation of the dimeric POM was rationalized by means of DFT calculations. The dissociation process is unfavorable in bulk water, but becomes favorable in the protein-POM complex due to the low dielectric response at the protein surface. The crystal structure shows that the monomeric form is stabilized by electrostatic and water-mediated hydrogen bonding interactions with the protein. It interacts at three distinct sites, close to the aspartate-containing hydrolysis sites, demonstrating high selectivity towards peptide bonds containing this residue.

Keywords: co-crystallization; density functional calculations; dielectric distribution; polyoxometalates; protein-assisted dissociation.