Structural and functional aspects of metal binding sites in natural and designed metalloproteins

The chapter discusses the main properties of metal ions in proteins. First, it describes the amino acids that act as ligands and their possible binding modes. The most representative metal ions in biological systems are briefly outlined, mainly regarding their preferred geometry and their functions. Finally, the chapter focuses on two classes of iron-containing metalloproteins (heme proteins and carboxylate-bridged diiron proteins) in order to illustrate how the same metal cofactor can be engaged in a number of different roles. The various first and second ligation sphere interactions, which finely tune the cofactor properties, thus effecting such different functions, will be highlighted. The models developed by us for these two classes of metalloproteins will be also described, summarizing principles and methods for designing artificial metalloproteins.