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Structural insights into simocyclinone as an antibiotic, effector ligand and substrate.


ABSTRACT: Simocyclinones are antibiotics produced by Streptomyces and Kitasatospora species that inhibit the validated drug target DNA gyrase in a unique way, and they are thus of therapeutic interest. Structural approaches have revealed their mode of action, the inducible-efflux mechanism in the producing organism, and given insight into one step in their biosynthesis. The crystal structures of simocyclinones bound to their target (gyrase), the transcriptional repressor SimR and the biosynthetic enzyme SimC7 reveal fascinating insight into how molecular recognition is achieved with these three unrelated proteins.

SUBMITTER: Buttner MJ 

PROVIDER: S-EPMC5812520 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Structural insights into simocyclinone as an antibiotic, effector ligand and substrate.

Buttner Mark J MJ   Schäfer Martin M   Lawson David M DM   Maxwell Anthony A  

FEMS microbiology reviews 20180101 1


Simocyclinones are antibiotics produced by Streptomyces and Kitasatospora species that inhibit the validated drug target DNA gyrase in a unique way, and they are thus of therapeutic interest. Structural approaches have revealed their mode of action, the inducible-efflux mechanism in the producing organism, and given insight into one step in their biosynthesis. The crystal structures of simocyclinones bound to their target (gyrase), the transcriptional repressor SimR and the biosynthetic enzyme S  ...[more]

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