2A6H

Crystal structure of the T. thermophilus RNA polymerase holoenzyme in complex with antibiotic sterptolydigin

Summary for 2A6H

• Entry DOI: 10.2210/pdb2a6h/pdb
• Related: 1IW7 1SMY 2A68 2A69 2A6E
• 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, streptolydigin, antibiotic, transcription regulation, riken structural genomics/proteomics initiative, rsgi, structural genomics, transferase
• Biological source: Thermus thermophilus; More
• Cellular location: Cytoplasm : Q5SKW1
• Total number of polymer chains: 12
• Total formula weight: 854782.62

Authors

Temiakov, D.,Zenkin, N.,Vassylyeva, M.N.,Perederina, A.,Tahirov, T.H.,Savkina, M.,Zorov, S.,Nikiforov, V.,Igarashi, N.,Matsugaki, N.,Wakatsuki, S.,Severinov, K.,Vassylyev, D.G.,RIKEN Structural Genomics/Proteomics Initiative (RSGI) (deposition date: 2005-07-02, release date: 2005-09-20, Last modification date: 2023-08-23)

Primary citation

Temiakov, D.,Zenkin, N.,Vassylyeva, M.N.,Perederina, A.,Tahirov, T.H.,Kashkina, E.,Savkina, M.,Zorov, S.,Nikiforov, V.,Igarashi, N.,Matsugaki, N.,Wakatsuki, S.,Severinov, K.,Vassylyev, D.G.
Structural basis of transcription inhibition by antibiotic streptolydigin.
Mol.Cell, 19:655-666, 2005

PubMed Abstract: Streptolydigin (Stl) is a potent inhibitor of bacterial RNA polymerases (RNAPs). The 2.4 A resolution structure of the Thermus thermophilus RNAP-Stl complex showed that, in full agreement with the available genetic data, the inhibitor binding site is located 20 A away from the RNAP active site and encompasses the bridge helix and the trigger loop, two elements that are considered to be crucial for RNAP catalytic center function. Structure-based biochemical experiments revealed additional determinants of Stl binding and demonstrated that Stl does not affect NTP substrate binding, DNA translocation, and phosphodiester bond formation. The RNAP-Stl complex structure, its comparison with the closely related substrate bound eukaryotic transcription elongation complexes, and biochemical analysis suggest an inhibitory mechanism in which Stl stabilizes catalytically inactive (preinsertion) substrate bound transcription intermediate, thereby blocking structural isomerization of RNAP to an active configuration. The results provide a basis for a design of new antibiotics utilizing the Stl-like mechanism.

PubMed: 16167380
DOI: 10.1016/j.molcel.2005.07.020

Experimental method

X-RAY DIFFRACTION (2.4 Å)