Inhibition of bacterial RNA polymerase by streptolydigin: Stabilization of a straight-bridge-helix active-center conformation

Steven Tuske, Stefan G. Sarafianos, Xinyue Wang, Brian Hudson, Elena Sineva, Jayanta Mukhopadhyay, Jens J. Birktoft, Olivier Leroy, Sajida Ismail, Arthur D. Clark, Chhaya Dharia, Andrew Napoli, Oleg Laptenko, Jookyung Lee, Sergei Borukhov, Richard H. Ebright, Eddy Arnold

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153 Scopus citations

Abstract

We define the target, mechanism, and structural basis of inhibition of bacterial RNA polymerase (RNAP) by the tetramic acid antibiotic streptolydigin (Stl). Stl binds to a site adjacent to but not overlapping the RNAP active center and stabilizes an RNAP-active-center conformational state with a straight-bridge helix. The results provide direct support for the proposals that alternative straight-bridge-helix and bent-bridge-helix RNAP-active-center conformations exist and that cycling between straight-bridge-helix and bent-bridge-helix RNAP-active-center conformations is required for RNAP function. The results set bounds on models for RNAP function and suggest strategies for design of novel antibacterial agents.

Original languageEnglish (US)
Pages (from-to)541-552
Number of pages12
JournalCell
Volume122
Issue number4
DOIs
StatePublished - Aug 16 2005

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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    Tuske, S., Sarafianos, S. G., Wang, X., Hudson, B., Sineva, E., Mukhopadhyay, J., Birktoft, J. J., Leroy, O., Ismail, S., Clark, A. D., Dharia, C., Napoli, A., Laptenko, O., Lee, J., Borukhov, S., Ebright, R. H., & Arnold, E. (2005). Inhibition of bacterial RNA polymerase by streptolydigin: Stabilization of a straight-bridge-helix active-center conformation. Cell, 122(4), 541-552. https://doi.org/10.1016/j.cell.2005.07.017