Advances in Bacterial Methionine Aminopeptidase Inhibition

Title:Advances in Bacterial Methionine Aminopeptidase Inhibition

Volume: 16 Issue: 4

Author(s): Travis R. Helgren, Phumvadee Wangtrakuldee, Bart L. Staker and Timothy J. Hagen

Affiliation:

Keywords: Antibacterial, Metalloenzyme, Methionine aminopeptidase (MetAP), Protein crystal structure.

Abstract: 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.

Cite this article as:

Helgren R. Travis, Wangtrakuldee Phumvadee, Staker L. Bart and Hagen J. Timothy, Advances in Bacterial Methionine Aminopeptidase Inhibition, Current Topics in Medicinal Chemistry 2016; 16 (4) . https://dx.doi.org/10.2174/1568026615666150813145410