Iron center, substrate recognition and mechanism of peptide deformylase

Eubacterial proteins are synthesized with a formyl group at the N-terminus which is hydrolytically removed from the nascent chain by the mononuclear i ron enzyme peptide deformylase. Catalytic efficiency strongly depends on th e identity of the bound metal. We have determined by X-ray crystallography the Fe2+, Ni2+ and Zn2+ forms of the Escherichia coli enzyme and a structur e in complex with the reaction product Met-Ala-Ser. The structure of the co mplex, with the tripeptide bound at the active site, suggests detailed mode ls for the mechanism of substrate recognition and catalysis. Differences of the protein structures due to the identity of the bound metal are extremel y small and account only for the observation that Zn2+ binds more tightly t han Fe2+ or Ni2+. The striking loss of catalytic activity of the Zn2+ form could be caused by its reluctance to change between tetrahedral and five-fo ld metal coordination believed to occur during catalysis.