Zinc plays a key role in human and bacterial GTP cyclohydrolase I

The crystal structure of recombinant human GTP cyclohydrolase I was solved by Patterson search methods by using the coordinates of the Escherichia col i enzyme as a model. The human as well as bacterial enzyme were shown to co ntain an essential zinc ion coordinated to a His side chain and two thiol g roups in each active site of the homodecameric enzymes that had escaped det ection during earlier studies of the E. coli enzyme. The zinc ion is propos ed to generate a hydroxyl nucleophile for attack of imidazole ring carbon a tom eight of the substrate, GTP, It may also be involved in the hydrolytic release of formate from the intermediate, 2-amino-5-formylamino-6-ribosylam ino-4(3H)-pyrimidinone 5'-triphosphate, and in the consecutive Amadori rear rangement of the ribosyl moiety.