Kehl-Fie, T.E.; Waldron, K.J.

Nat. Commun. 2020, 11, 10.1038/s41467-020-16478-0

AbstractAlmost half of all enzymes utilize a metal cofactor. However, the features that dictate the metal utilized by metalloenzymes are poorly understood, limiting our ability to manipulate these enzymes for industrial and health-associated applications. The ubiquitous iron/manganese superoxide dismutase (SOD) family exemplifies this deficit, as the specific metal used by any family member cannot be predicted. Biochemical, structural and paramagnetic analysis of two evolutionarily related SODs with different metal specificity produced by the pathogenic bacterium Staphylococcus aureus identifies two positions that control metal specificity. These residues make no direct contacts with the metal-coordinating ligands but control the metal’s redox properties, demonstrating that subtle architectural changes can dramatically alter metal utilization. Introducing these mutations into S. aureus alters the ability of the bacterium to resist superoxide stress when metal starved by the host, revealing that small changes in metal-dependent activity can drive the evolution of metalloenzymes with new cofactor specificity.

Salmain, M.; Thorimbert, S.

Eur. J. Inorg. Chem. 2017, 2017, 3622-3634, 10.1002/ejic.201700365

Several prochiral NCN‐pincer complexes of palladium(II), with hemilabile ligands and a long aliphatic chain, were synthesized and characterized spectroscopically. In some of the complexes, the presence of two different substituents on the N donor atoms made them stereogenic, so that they were isolated as a mixture of diastereoisomers, which could be differentiated by 1H NMR spectroscopy. Binding of some of these complexes to bovine β‐lactoglobin by insertion within its inner cavity was theoretically investigated by molecular‐docking simulations and was experimentally confirmed by CD spectroscopy. Adjunction of H‐bond donor substituents on the ligand framework gave more‐stable supramolecular protein–complex assemblies. These constructs were shown to catalyze aldol condensation reactions in aqueous media, affording, in some cases, the less‐favorable cis product. Since the corresponding complexes exclusively gave the trans product in the absence of β‐lactoglobulin, this unusual diastereoselectivity was ensued by the second sphere of coordination brought by the protein host.