Methionine aminopeptidases (MetAPs) are metalloenzymes that cleave the N-terminal methionine
from newly synthesized peptides and proteins. These MetAP enzymes are present in bacteria,
and knockout experiments have shown that MetAP activity is essential for cell life, suggesting that
MetAPs are good antibacterial drug targets. MetAP enzymes are also present in the human host and
selectivity is essential. There have been significant structural biology efforts and over 65 protein crystal
structures of bacterial MetAPs are deposited into the PDB. This review highlights the available
crystallographic data for bacterial MetAPs. Structural comparison of bacterial MetAPs with human
MetAPs highlights differences that can lead to selectivity. In addition, this review includes the chemical diversity of
molecules that bind and inhibit the bacterial MetAP enzymes. Analysis of the structural biology and chemical space of
known bacterial MetAP inhibitors leads to a greater understanding of this antibacterial target and the likely development
of potential antibacterial agents.
Keywords: Antibacterial, Metalloenzyme, Methionine aminopeptidase (MetAP), Protein crystal structure.
Rights & PermissionsPrintExport