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Curr Opin Microbiol. 2011 Oct;14(5):532-43. doi: 10.1016/j.mib.2011.07.030. Epub 2011 Aug 19.

New target for inhibition of bacterial RNA polymerase: 'switch region'.

Author information

1
Howard Hughes Medical Institute, Waksman Institute, and Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA.

Abstract

A new drug target - the 'switch region' - has been identified within bacterial RNA polymerase (RNAP), the enzyme that mediates bacterial RNA synthesis. The new target serves as the binding site for compounds that inhibit bacterial RNA synthesis and kill bacteria. Since the new target is present in most bacterial species, compounds that bind to the new target are active against a broad spectrum of bacterial species. Since the new target is different from targets of other antibacterial agents, compounds that bind to the new target are not cross-resistant with other antibacterial agents. Four antibiotics that function through the new target have been identified: myxopyronin, corallopyronin, ripostatin, and lipiarmycin. This review summarizes the switch region, switch-region inhibitors, and implications for antibacterial drug discovery.

PMID:
21862392
PMCID:
PMC3196380
DOI:
10.1016/j.mib.2011.07.030
[Indexed for MEDLINE]
Free PMC Article

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