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Iron center, substrate recognition and mechanism of peptide deformylase

Abstract

Eubacterial proteins are synthesized with a formyl group at the N-terminus which is hydrolytically removed from the nascent chain by the mononuclear iron enzyme peptide deformylase. Catalytic efficiency strongly depends on the identity of the bound metal. We have determined by X-ray crystallography the Fe 2+ , Ni 2+ and Zn 2+ forms of the Escherichia coli enzyme and a structure in complex with the reaction product Met-Ala-Ser. The structure of the complex, with the tripeptide bound at the active site, suggests detailed models for the mechanism of substrate recognition and catalysis. Differences of the protein structures due to the identity of the bound metal are extremely small and account only for the observation that Zn 2+ binds more tightly than Fe 2+ or Ni 2+ . The striking loss of catalytic activity of the Zn 2+ form could be caused by its reluctance to change between tetrahedral and five-fold metal coordination believed to occur during catalysis.

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Figure 1: a, Omit map of Met-Ala-Ser in the PDF–Ni/MAS structure contoured at 1σ .
Figure 2: Peptide deformylase in complex with the reaction product Met-Ala-Ser.
Figure 3

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Acknowledgements

We thank D. Madden, K. Fritz-Wolf and K. Scheffzek for critical discussions and help at various stages of the project, H. Wagner for excellent maintenance of the X-ray facilities at the MPI Heidelberg, I. Dehof for help with the figures, and K. Holmes and J. Knappe for continuous support.

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Correspondence to Wolfgang Kabsch.

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Becker, A., Schlichting, I., Kabsch, W. et al. Iron center, substrate recognition and mechanism of peptide deformylase . Nat Struct Mol Biol 5, 1053–1058 (1998). https://doi.org/10.1038/4162

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