InterPro domain: IPR036821

Peptide deformylase (PDF) is an essential metalloenzyme required for the removal of the formyl group at the N terminus of nascent polypeptide chains in eubacteria: 3.5.1.88 [ 1 ]. The enzyme acts as a monomer and binds a single metal ion, catalysing the reaction: N-formyl-L-methionine + H ₂ O = formate + methionyl peptide Catalytic efficiency strongly depends on the identity of the bound metal [ 2 ].

The structure of these enzymes is known [ 3 , 4 ]. PDF, a zinc metalloenzyme from the mitochondrion, comprises an active core domain of 147 residues and a C-terminal tail of 21 residue. The 3D fold of the catalytic core has been determined by X-ray crystallography and NMR. Overall, the structure contains a series of anti-parallel beta-strands that surround two perpendicular alpha-helices. The C-terminal helix contains the characteristic HEXXH motif of metalloenzymes, which is crucial for activity. The helical arrangement, and the way the histidine residues bind the zinc ion, is reminiscent of metalloproteases such as thermolysin or metzincins. However, the arrangement of secondary and tertiary structures of PDF, and the positioning of its third zinc ligand (a cysteine residue), are quite different. These discrepancies, together with notable biochemical differences, suggest that PDF constitutes a new class of zinc-metalloenzymes [ 5 ].

These enzymes utilize Fe(II) as the catalytic metal ion, which can be replaced with a nickel or cobalt ion with no loss of activity. There are two types of peptide deformylases, types I and II, which differ in structure only in the outer surface of the domain. Because these enzymes are essential only in prokaryotes (although eukaryotic gene sequences have been found), they are a target for a new class of antibacterial agents [ 5 , 6 , 7 , 8 ].

1. Iron center, substrate recognition and mechanism of peptide deformylase. Nat. Struct. Biol. 5, 1053-8
2. Structure of peptide deformylase and identification of the substrate binding site. J. Biol. Chem. 273, 11413-6
3. A new subclass of the zinc metalloproteases superfamily revealed by the solution structure of peptide deformylase. J. Mol. Biol. 262, 375-86
4. Solution structure of nickel-peptide deformylase. J. Mol. Biol. 280, 501-13
5. Organellar peptide deformylases: universality of the N-terminal methionine cleavage mechanism. Trends Plant Sci. 6, 566-72
6. Peptide deformylase as a target for new generation, broad spectrum antimicrobial agents. Mol. Microbiol. 36, 1197-205
7. The crystal structures of four peptide deformylases bound to the antibiotic actinonin reveal two distinct types: a platform for the structure-based design of antibacterial agents. J. Mol. Biol. 320, 951-62
8. Structure analysis of peptide deformylases from Streptococcus pneumoniae, Staphylococcus aureus, Thermotoga maritima and Pseudomonas aeruginosa: snapshots of the oxygen sensitivity of peptide deformylase. J. Mol. Biol. 330, 309-21