Direct observation of the Zr^IV inter­action with the carboxamide bond in a noncovalent complex between Hen Egg White Lysozyme and a Zr-substituted Keggin polyoxometalate

The successful cocrystallization of the noncovalent complex formed between (Et₂NH₂)₈[{α-PW₁₁O₃₉Zr-(μ-OH)(H₂O)}₂]·7H₂O Keggin polyoxometalate (2) and Hen Egg White Lysozyme (HEWL) protein is reported. The resulting structural model revealed inter­action between monomeric [Zr(PW₁₁O₃₉)]⁴⁻(1), which is a postulated catalytically active species, and the protein in two positions in the asymmetric unit. The first position (occupancy 36%) confirms the previously observed binding sites on the protein surface, whereas the second position (occupancy 14%) provides novel insights into the hydrolytic mechanisms of Zr^IV-substituted polyoxometalates. The new inter­action site occurs at the Asn65 residue, which is directly next to the Asp66–Gly67 peptide bond that was identified recently as a cleavage site in the polyoxometalate-catalysed hydrolysis of HEWL. Furthermore, in this newly discovered binding site, the monomeric polyoxometalate 1 is observed to bind directly to the side chain of the Asn65 residue. This binding of Zr^IV as a Lewis-acid metal to the carbonyl O atom of the Asn65 side chain is very similar to the inter­mediate state proposed in density functional theory (DFT) studies in which Zr^IV activates the peptide bond via inter­action with its carbonyl O atom, and can be thus regarded as a model for inter­action between Zr^IV and a peptide bond.