Protein metalation by metal-based drugs: X-ray crystallography and mass spectrometry studies

The combined use of X-ray crystallography and mass spectrometry represents a valuable strategy to investigate and characterize protein metalation induced by anticancer metal-based drugs. Here, we summarize a series of significant results recently obtained in our laboratories upon the examination of the structures of several adducts of proteins with representative metallodrugs (mostly containing ruthenium, gold and platinum). The general mechanisms of protein metalation that emerge from a careful comparative analysis of these structures are illustrated and their mechanistic implications are discussed. Possible directions for future work in the field are delineated.