Methionine aminopeptidase (Escherichia coli) (MetAP)

Methionine aminopeptidase (MetAP) from Escherichia coli is a critical metalloenzyme that catalyzes the removal of the initiator N-terminal methionine from nascent proteins (UniProt: P0AE18). This process, known as N-terminal methionine excision (NME), is a universal and essential post-translational modification required for proper protein maturation, stability, and functional activity (PubMed: 10764577). In E. coli, MetAP is encoded by the essential map gene, making it an attractive target for the design of new classes of antibiotics (PubMed: 16212311). Small molecule inhibitors, such as the natural product actinonin and various synthetic hydroxamates, target the enzyme's active site, which typically coordinates two metal ions, usually cobalt or manganese (PubMed: 9587011). Blocking MetAP activity leads to the retention of the N-terminal methionine, resulting in misfolded or inactive proteins and subsequent bacterial cell death. Therapeutic development focuses on achieving high selectivity to avoid inhibiting human MetAP1 and MetAP2, which could lead to adverse effects in the host (PubMed: 15149174).

Other names

MetAP1Peptidase Mmap gene productN-terminal methionine aminopeptidase

Inhibition of the enzymatic removal of the N-terminal methionine from nascent proteins, which disrupts protein maturation and leads to bacterial cell death or growth arrest (PubMed: 10764577).