Targeting the role of N-terminal methionine processing enzymes in Mycobacterium tuberculosis.
The discovery of anti-tuberculosis agents that target new pathways is crucial for effective short-term TB therapy that will limit the development of resistance. The clinical significance of multidrug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis, latent TB and Human Immunodeficiency Virus co-infection in tuberculosis patients have made the development of new antimycobacterials more imperative. A better understanding of the major pathways that are involved in the pathogenesis, survival, and dormancy of Mtb will aid in the identification of new drug targets. Here, we review the N-terminal methionine excision (NME) pathway as a potential drug target during host infection with M. tuberculosis. The removal of the N-terminal methionine is a requirement for some proteins prior to post-translational modifications and processing. Therefore, an understanding of the physiological relevance of the two families of enzymes at the center of NME - peptide deformylases and methionine aminopeptidases - has the prospect of adding novel targets and antimycobacterials to the pipeline.
Olaleye
Omonike A
OA
College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004, USA. Olaleyeoa@tsu.edu
Bishai
William R
WR
Liu
Jun O
JO
D000581:Amidohydrolases / Q000494:pharmacology*; D000626:Aminopeptidases / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000494:pharmacology*; D055808:Drug Discovery; D006801:Humans; D063208:Methionyl Aminopeptidases; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology
D000995:Antitubercular Agents; D000626:Aminopeptidases; D063208:Methionyl Aminopeptidases; D000581:Amidohydrolases; C084507:peptide deformylase