Advances in Bacterial Methionine Aminopeptidase Inhibition

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

Journal Name: Current Topics in Medicinal Chemistry

Volume 16 , Issue 4 , 2016

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Graphical 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.

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

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Article Details

Year: 2016
Published on: 14 October, 2015
Page: [397 - 414]
Pages: 18
DOI: 10.2174/1568026615666150813145410
Price: $65

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