Recent advances in protein metalation: structural studies

Protein metalation is a process that determines the formation of adducts upon reaction of metal compounds with proteins. Protein metalation plays a crucial role in different fields, determining the mechanism of action and toxicity of metal-based drugs and the basis for the rational design of artificial metalloenzymes and protein-based metallodrug-delivery systems. Recent advances in structural studies unveiling the basis of the metal compounds/protein recognition process are briefly discussed here. The analysis of the structures of Pt, Au, Ru, Re, Pd, Ir, Os, Rh and Pt-As/protein adducts reveals that metal compounds (i) can bind proteins via non-covalent interactions or via coordination to selected residue side chains upon the release of labile ligands; (ii) can undergo reduction/oxidation processes upon protein binding that in turn can lead to changes in the metal coordination sphere and breakdown of the metal compound; (iii) can bind different protein recognition sites with a preference for selected side chains that is governed by hard and soft acids and bases, and with the number and type of binding sites changing over time; and (iv) can retain a certain degree of flexibility and reactivity in the final metal/protein adduct.

Automated summary

Protein metalation is the process of forming adducts when metal compounds react with proteins, which plays a crucial role in determining the mechanism of metal-based drugs and the design of artificial metalloenzymes. Recent advances in structural studies have revealed the recognition process between metal compounds and proteins.