Structural basis for transcription inhibition by tagetitoxin

Dmitry G. Vassylyev, Vladimir Svetlov, Marina N. Vassylyeva, Anna Perederina, Noriyuki Igarashi, Naohiro Matsugaki, Soichi Wakatsuki, Irina Artsimovitch

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


Tagetitoxin (Tgt) inhibits transcription by an unknown mechanism. A structure at a resolution of 2.4 Å of the Thermus thermophilus RNA polymerase (RNAP)-Tgt complex revealed that the Tgt-binding site within the RNAP secondary channel overlaps that of the stringent control effector ppGpp, which partially protects RNAP from Tgt inhibition. Tgt binding is mediated exclusively through polar interactions with the β and β′ residues whose substitutions confer resistance to Tgt in vitro. Importantly, a Tgt phosphate, together with two active site acidic residues, coordinates the third Mg 2+ ion, which is distinct from the two catalytic metal ions. We show that Tgt inhibits all RNAP catalytic reactions and propose a mechanism in which the Tgt-bound Mg2+ ion has a key role in stabilization of an inactive transcription intermediate. Remodeling of the active site by metal ions could be a common theme in the regulation of catalysis by nucleic acid enzymes.

Original languageEnglish (US)
Pages (from-to)1086-1093
Number of pages8
JournalNature Structural and Molecular Biology
Issue number12
StatePublished - Dec 27 2005

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology


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