2A68

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

2A68 の概要

• エントリーDOI: 10.2210/pdb2a68/pdb
• 関連するPDBエントリー: 1IW7 1SMY 2a69 2a6e 2a6h
• 分子名称: DNA-directed RNA polymerase alpha chain, DNA-directed RNA polymerase beta chain, DNA-directed RNA polymerase beta' chain, ... (9 entities in total)
• 機能のキーワード: rna polymerase holoenzyme, rifabutin, antibiotic, transcription regulation, riken structural genomics/proteomics initiative, rsgi, structural genomics, transferase
• 由来する生物種: Thermus thermophilus; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 868886.03

構造登録者

Artsimovitch, I.,Vassylyeva, M.N.,Svetlov, D.,Svetlov, V.,Perederina, A.,Igarashi, N.,Matsugaki, N.,Wakatsuki, S.,Tahirov, T.H.,Vassylyev, D.G.,RIKEN Structural Genomics/Proteomics Initiative (RSGI) (登録日: 2005-07-01, 公開日: 2005-09-20, 最終更新日: 2023-08-23)

主引用文献

Artsimovitch, I.,Vassylyeva, M.N.,Svetlov, D.,Svetlov, V.,Perederina, A.,Igarashi, N.,Matsugaki, N.,Wakatsuki, S.,Tahirov, T.H.,Vassylyev, D.G.
Allosteric modulation of the RNA polymerase catalytic reaction is an essential component of transcription control by rifamycins.
Cell(Cambridge,Mass.), 122:351-363, 2005

PubMed Abstract: Rifamycins, the clinically important antibiotics, target bacterial RNA polymerase (RNAP). A proposed mechanism in which rifamycins sterically block the extension of nascent RNA beyond three nucleotides does not alone explain why certain RNAP mutations confer resistance to some but not other rifamycins. Here we show that unlike rifampicin and rifapentin, and contradictory to the steric model, rifabutin inhibits formation of the first and second phosphodiester bonds. We report 2.5 A resolution structures of rifabutin and rifapentin complexed with the Thermus thermophilus RNAP holoenzyme. The structures reveal functionally important distinct interactions of antibiotics with the initiation sigma factor. Strikingly, both complexes lack the catalytic Mg2+ ion observed in the apo-holoenzyme, whereas an increase in Mg2+ concentration confers resistance to rifamycins. We propose that a rifamycin-induced signal is transmitted over approximately 19 A to the RNAP active site to slow down catalysis. Based on structural predictions, we designed enzyme substitutions that apparently interrupt this allosteric signal.

PubMed: 16096056
DOI: 10.1016/j.cell.2005.07.014

実験手法

X-RAY DIFFRACTION (2.5 Å)