Crystal Structure of Human Arginase I Complexed with Thiosemicarbazide Reveals an Unusual Thiocarbonyl μ-Sulfide Ligand in the Binuclear Manganese Cluster

The crystal structure of the human arginase I−thiosemicarbazide complex reveals an unusual thiocarbonyl μ-sulfide ligand in the binuclear manganese cluster. The CS moiety of thiosemicarbazide bridges Mn²⁺_A and Mn²⁺_B with coordination distances of 2.6 and 2.4 Å, respectively. Otherwise, the binding of thiosemicarbazide to human arginase I does not cause any significant structural changes in the active site. The crystal structure of the unliganded enzyme reveals a hydrogen-bonded water molecule that could support proton transfer between a μ-water molecule and H141 to regenerate the nucleophilic μ-hydroxide ion in the final step of catalysis.