deformylase

Deformylase is an enzyme that catalyzes the removal of a formyl group from a substrate. The best-known member is peptide deformylase (PDF; EC 3.5.1.88), which acts on N-formylmethionyl groups that mark many newly synthesized proteins in numerous bacteria and in some plastids. By removing the N-formyl group from the initiator residue, PDF enables subsequent processing steps that mature the protein, such as removal of the initiator methionine when appropriate.

Substrates and reaction: PDF recognizes N-formylated methionine at the N-terminus of nascent polypeptides. It hydrolyzes the formylated peptide bond, yielding a deformylated polypeptide and formate. This deformylation is a common step in bacterial protein maturation and can influence the efficiency and fidelity of downstream processing.

Mechanism and structure: Peptide deformylase is a metal-dependent metalloprotease, typically requiring a divalent metal ion such as Zn2+ in its active site. Conserved residues coordinate the metal and activate a water molecule for nucleophilic attack on the formyl carbon. Some PDFs can also utilize Mn2+ or Co2+ in vitro, with implications for inhibitor design. The enzyme is generally small and cytosolic in bacteria, and structural studies reveal a single-domain metalloenzyme architecture with a characteristic active-site configuration.

Biological and clinical significance: PDF is essential for the maturation of many bacterial proteins and is considered a potential antibiotic target. Inhibitors such as actinonin and related compounds can block deformylation and impair bacterial growth. Because PDFs are not present in most human cytosolic translation systems, selective inhibitors have drawn interest as antimicrobial agents. Resistance and variability among species can influence efficacy.

Distribution: Peptide deformylases are widespread in bacteria and are also found in the plastids of plants and some algae. In contrast, deformylases of this type are generally absent from animal cytosol, reflecting differences in initiator methionine processing between domains of life.