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Metal-mediated inhibition is a viable approach for inhibiting cellular methionine aminopeptidase.

ABSTRACT: Methionine aminopeptidase (MetAP) plays an essential role for cell survival. Hence, MetAP is a promising target for developing broad spectrum antibacterial agents. MetAP can be activated in vitro by a number of divalent metals, and X-ray structures show that the active site can accommodate two cations. Herein, we demonstrate bacterial growth inhibition by a compound that targets MetAP by recruitment of a third auxiliary metal. Contrary to previous beliefs, this shows that metal-mediated inhibition is a viable approach for discovering MetAP inhibitors that are effective for therapeutic application.

SUBMITTER: Chai SC

PROVIDER: S-EPMC2783975 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Metal-mediated inhibition is a viable approach for inhibiting cellular methionine aminopeptidase.

Chai Sergio C SC Ye Qi-Zhuang QZ

Bioorganic & medicinal chemistry letters 20091023 24

Methionine aminopeptidase (MetAP) plays an essential role for cell survival. Hence, MetAP is a promising target for developing broad spectrum antibacterial agents. MetAP can be activated in vitro by a number of divalent metals, and X-ray structures show that the active site can accommodate two cations. Herein, we demonstrate bacterial growth inhibition by a compound that targets MetAP by recruitment of a third auxiliary metal. Contrary to previous beliefs, this shows that metal-mediated inhibiti ...[more]

PMID: 19889537

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