Binding of metal cyanide complexes to bovine liver rhodanese in the crystalline state.

Bovine liver rhodanese, which catalyzes the transfer of sulfur atoms between a variety of sulfur donor and sulfur acceptor substrates, is inhibited by metal cyanide complexes [Volini, M., Van Sweringen, B., & Chen, F.-Sh. (1978) Arch. Biochem. Biophys. 191, 205-215]. Crystallographic studies are described which reveal the binding mode of four different metal cyanides to bovine liver rhodanese: Na[Au(CN2], K2[Pt(CN)4], K2[Ni(CN)4], and K2[Zn(CN)4]. It appears that these complexes bind at one common site at the entrance of the active site pocket, interacting with the positively charged side chains of Arg-186 and Lys-249. This observation explains the inhibition of rhodanese by this class of compounds. For the platinum and nickel cyanide complexes virtually no other binding sites are observed. The gold complex binds, however, to three additional cysteine residues, thereby also displacing the extra sulfur atom which was bound to the essential Cys-247 in the sulfur-rhodanese complex. The zinc complex binds to completely different additional sites and forms complexes with the side chains of Asp-101 and His-203. Possible reasons for these different binding modes are discussed in terms of the preference for "hard" and "soft" ligands of these four metal ions.