Structural Characterization of the Complex between Hen Egg‐White Lysozyme and Zr^IV‐Substituted Keggin Polyoxometalate as Artificial Protease

Abstract

Successful co-crystallization of a noncovalent complex between hen egg-white lysozyme (HEWL) and the monomeric Zr(IV) -substituted Keggin polyoxometalate (POM) (Zr1 K1), (Et2 NH2)3 [Zr(PW11 O39)] (1), has been achieved, and its single-crystal X-ray structure has been determined. The dimeric Zr(IV) -substituted Keggin-type polyoxometalate (Zr1 K2), (Et2 NH2)10 [Zr(PW11 O39 )2] (2), has been previously shown to exhibit remarkable selectivity towards HEWL hydrolysis. The reported X-ray structure shows that the hydrolytically active Zr(IV) -substituted Keggin POM exists as a monomeric species. Prior to hydrolysis, this monomer interacts with HEWL in the vicinity of the previously identified cleavage sites found at Trp28-Val29 and Asn44-Arg45, through water-mediated H-bonding and electrostatic interactions. Three binding sites are observed at the interface of the negatively charged Keggin POM and the positively charged regions of HEWL at: 1) Gly16, Tyr20, and Arg21; 2) Asn44, Arg45, and Asn46; and 3) Arg128.

Tuning the Selectivity and Reactivity of Metal‐Substituted Polyoxometalates as Artificial Proteases by Varying the Nature of the Embedded Lewis Acid Metal Ion

“…In aqueous solutions the Ce1–K2, Zr1–K2 and Zr2–K2 POMs are prone to form equilibria and dissociate into monomeric species, which are presumed to be the effective catalysts in the hydrolysis of the peptide bond (see Figures and ) , . Equilibria between different POM species can exist in solution depending on factors such as POM concentration, temperature, pH and incubation time .…”

Hydrolysis of chemically distinct sites of human serum albumin by polyoxometalate: A hybrid QM/MM (ONIOM) study

“…The structures of ZrK and HSA were obtained from the Protein Data Bank (PDB ID: 4XYY and 4K2C, respectively) . The starting structures of all ZrK‐HSA complexes were taken from our previous molecular dynamic (MD) simulations.…”

“…) . Furthermore, a co‐crystal structure of monomeric ZrK with another biomolecule (HEWL) was resolved recently …”

“…Structure of the polyoxometalate (ZrK)—human serum albumin (HSA) complex. The structures of ZrK and HSA are based on their X‐ray structures . [Color figure can be viewed at wileyonlinelibrary.com]…”

“…Additionally, this ion has been proposed to play similar roles in the hydrolysis of esters, phosphoesters, and nitriles . The Zr ion of ZrK also exhibits significant hydrolytic activity, due to its properties like high Lewis acidity, redox stability, and oxophilicity . Additionally, it displays fast ligand exchange kinetics and is kinetically and stereochemically labile .…”