The interaction of rhodium compounds with proteins: A structural overview

Rhodium compounds have been used as scaffold for enzyme inhibitors, modulators of protein/protein interactions and of protein aggregation. These compounds have been investigated in their reaction with peptides and proteins with the aim to create artificial metalloenzymes with enhanced catalytic features. Despite several studies have been carried out in this context, the interactions occurring between Rh compounds and these biological molecules and the mechanisms that are responsible for the formation of Rh/peptides and Rh/protein adducts are still largely unknown. This review describes and analyzes the known structures of complexes between protein and Rh compounds and of Rh/protein adducts deposited in the Protein Data Bank. Artificial metalloenzymes are frequently formed by anchoring Rh compounds to proteins via covalent linkage strategies. However, new biohybrids can also be formed by dative anchoring, since coordinative bonds of protein residue side chains with Rh centers (and non-covalent interactions between protein atoms and Rh ligands) can occur. In these adducts, Rh centers preferentially bind the side chains of His, Asp, Asn, Lys and the C-terminal carboxylate. Our analysis provides interesting implications for the design of Rh-based artificial metalloenzymes.