First Crystal Structure of a Medicinally Relevant Gold Protein Complex: Unexpected Binding of [Au(PEt3)]+ to Histidine

Abstract

Unexpectedly, not interested in sulfur: the antiarthritic complex [Au(PEt3)Cl] (1) reacts with crystals of cyclophilin-3 (Cyp-3), a peptidyl prolyl isomerase enzyme linked to cellular stress responses, to form an Nε-bound [AuPEt3]+ adduct with the active site residue His 133, despite the presence of four Cys thiol groups in the protein. Complex 1 is a potent inhibitor of the enzyme (IC50=14 nM).