5UHC

Crystal structure of Mycobacterium tuberculosis transcription initiation complex containing 3nt RNA in complex with Rifampin

5UHC の概要

• エントリーDOI: 10.2210/pdb5uhc/pdb
• 関連するPDBエントリー: 5UH6 5UH7 5UH8 5UH9 5UHA 5UHB 5UHD 5UHE 5UHF 5UHG
• 分子名称: DNA-directed RNA polymerase subunit alpha, ZINC ION, MAGNESIUM ION, ... (11 entities in total)
• 機能のキーワード: rna polymerase complex, transcription, dna, rna, transcription-dna-rna complex, transcription/dna/rna
• 由来する生物種: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv); 詳細
• 細胞内の位置: Cytoplasm : P9WGI1
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 436219.29

構造登録者

Lin, W.,Das, K.,Feng, Y.,Ebright, R.H. (登録日: 2017-01-11, 公開日: 2017-04-12, 最終更新日: 2024-10-09)

主引用文献

Lin, W.,Mandal, S.,Degen, D.,Liu, Y.,Ebright, Y.W.,Li, S.,Feng, Y.,Zhang, Y.,Mandal, S.,Jiang, Y.,Liu, S.,Gigliotti, M.,Talaue, M.,Connell, N.,Das, K.,Arnold, E.,Ebright, R.H.
Structural Basis of Mycobacterium tuberculosis Transcription and Transcription Inhibition.
Mol. Cell, 66:169-179.e8, 2017

PubMed Abstract: Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, which kills 1.8 million annually. Mtb RNA polymerase (RNAP) is the target of the first-line antituberculosis drug rifampin (Rif). We report crystal structures of Mtb RNAP, alone and in complex with Rif, at 3.8-4.4 Å resolution. The results identify an Mtb-specific structural module of Mtb RNAP and establish that Rif functions by a steric-occlusion mechanism that prevents extension of RNA. We also report non-Rif-related compounds-Nα-aroyl-N-aryl-phenylalaninamides (AAPs)-that potently and selectively inhibit Mtb RNAP and Mtb growth, and we report crystal structures of Mtb RNAP in complex with AAPs. AAPs bind to a different site on Mtb RNAP than Rif, exhibit no cross-resistance with Rif, function additively when co-administered with Rif, and suppress resistance emergence when co-administered with Rif.

PubMed: 28392175
DOI: 10.1016/j.molcel.2017.03.001

実験手法

X-RAY DIFFRACTION (3.796 Å)