Structure and Activity of Human Mitochondrial Peptide Deformylase, a Novel Cancer Target Academic Article uri icon


MeSH Major

  • Amidohydrolases


  • Peptide deformylase proteins (PDFs) participate in the N-terminal methionine excision pathway of newly synthesized peptides. We show that the human PDF (HsPDF) can deformylate its putative substrates derived from mitochondrial DNA-encoded proteins. The first structural model of a mammalian PDF (1.7 A), HsPDF, shows a dimer with conserved topology of the catalytic residues and fold as non-mammalian PDFs. The HsPDF C-terminus topology and the presence of a helical loop (H2 and H3), however, shape a characteristic active site entrance. The structure of HsPDF bound to the peptidomimetic inhibitor actinonin (1.7 A) identified the substrate-binding site. A defined S1' pocket, but no S2' or S3' substrate-binding pockets, exists. A conservation of PDF-actinonin interaction across PDFs was observed. Despite the lack of true S2' and S3' binding pockets, confirmed through peptide binding modeling, enzyme kinetics suggest a combined contribution from P2'and P3' positions of a formylated peptide substrate to turnover.

publication date

  • April 17, 2009



  • Academic Article



  • eng

PubMed Central ID

  • PMC2782631

Digital Object Identifier (DOI)

  • 10.1016/j.jmb.2009.02.032

PubMed ID

  • 19236878

Additional Document Info

start page

  • 1211

end page

  • 28


  • 387


  • 5