Expression and characterization of Mycobacterium tuberculosis methionine aminopeptidase type 1a

Jing Ping Lu, Qi Zhuang Ye

Research output: Contribution to journalArticle

18 Scopus citations


Methionine aminopeptidase (MetAP) carries out the cotranslational N-terminal methionine excision and is essential for bacterial survival. Mycobacterium tuberculosis expresses two MetAPs, MtMetAP1a and MtMetAP1c, at different levels in growing and stationary phases, and both are potential targets to develop novel antitubercular therapeutics. Recombinant MtMetAP1a was purified as an apoenzyme, and metal binding and activation were characterized with an activity assay using a fluorogenic substrate. Ni(II), Co(II) and Fe(II) bound tightly at micromolar concentrations, and Ni(II) was the most efficient activator for the MetAP-catalyzed substrate hydrolysis. Although the characteristics of metal binding and activation are similar to MtMetAP1c we characterized before, MtMetAP1a was significantly more active, and more importantly, a set of inhibitors displayed completely different inhibitory profiles on the two mycobacterial MetAPs in both potency and metalloform selectivity. The differences in catalysis and inhibition predicted the significant differences in active site structure.

Original languageEnglish (US)
Pages (from-to)2776-2779
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Issue number9
StatePublished - May 1 2010


  • Antibacterial
  • Enzyme inhibitor
  • Metal cofactor
  • Metallohydrolase
  • Tuberculosis

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

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