2BE5

Crystal structure of the T. Thermophilus RNA polymerase holoenzyme in complex with inhibitor tagetitoxin

Summary for 2BE5

• Entry DOI: 10.2210/pdb2be5/pdb
• Related: 1IW7 1SMY 2A68 2A69 2A6E 2A6H
• Descriptor: DNA-directed RNA polymerase alpha chain, DNA-directed RNA polymerase beta chain, DNA-directed RNA polymerase beta' chain, ... (9 entities in total)
• Functional Keywords: rna polymerase holoenzyme, tagetitoxin, antibiotic, transcription regulation, riken structural genomics/proteomics initiative, rsgi, structural genomics, transferase
• Biological source: Thermus thermophilus; More
• Total number of polymer chains: 12
• Total formula weight: 854462.43

Authors

Vassylyev, D.G.,Svetlov, V.,Vassylyeva, M.N.,Perederina, A.,Igarashi, N.,Matsugaki, N.,Wakatsuki, S.,Artsimovitch, I.,RIKEN Structural Genomics/Proteomics Initiative (RSGI) (deposition date: 2005-10-22, release date: 2005-11-08, Last modification date: 2023-08-23)

Primary citation

Vassylyev, D.G.,Svetlov, V.,Vassylyeva, M.N.,Perederina, A.,Igarashi, N.,Matsugaki, N.,Wakatsuki, S.,Artsimovitch, I.
Structural basis for transcription inhibition by tagetitoxin
Nat.Struct.Mol.Biol., 12:1086-1093, 2005

PubMed Abstract: Tagetitoxin (Tgt) inhibits transcription by an unknown mechanism. A structure at a resolution of 2.4 A 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 beta and beta' 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 Mg(2+) 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.

PubMed: 16273103
DOI: 10.1038/nsmb1015

Experimental method

X-RAY DIFFRACTION (2.4 Å)