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

Cell. 2005 Aug 26;122(4):541-52. doi: 10.1016/j.cell.2005.07.017.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aminoglycosides / chemistry
  • Aminoglycosides / pharmacology*
  • Bacteria / enzymology*
  • Bacteria / genetics*
  • Binding Sites / drug effects
  • Binding Sites / physiology
  • DNA-Directed RNA Polymerases / antagonists & inhibitors*
  • DNA-Directed RNA Polymerases / chemistry
  • DNA-Directed RNA Polymerases / metabolism*
  • Feedback, Physiological / physiology
  • Models, Molecular
  • Molecular Structure
  • Protein Structure, Secondary / drug effects
  • Protein Structure, Secondary / genetics
  • RNA, Messenger / biosynthesis*


  • Aminoglycosides
  • RNA, Messenger
  • streptolydigin
  • DNA-Directed RNA Polymerases