4ZH4

Crystal structure of Escherichia coli RNA polymerase in complex with CBRP18

4ZH4 の概要

• エントリーDOI: 10.2210/pdb4zh4/pdb
• 関連するPDBエントリー: 4ZH2 4ZH3
• 分子名称: DNA-directed RNA polymerase subunit alpha, DNA-directed RNA polymerase subunit beta, DNA-directed RNA polymerase subunit beta', ... (8 entities in total)
• 機能のキーワード: rna polymerase, inhibitor, transcription, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 924087.82

構造登録者

Feng, Y.,Ebright, R.H. (登録日: 2015-04-24, 公開日: 2015-08-05, 最終更新日: 2023-09-27)

主引用文献

Feng, Y.,Degen, D.,Wang, X.,Gigliotti, M.,Liu, S.,Zhang, Y.,Das, D.,Michalchuk, T.,Ebright, Y.W.,Talaue, M.,Connell, N.,Ebright, R.H.
Structural Basis of Transcription Inhibition by CBR Hydroxamidines and CBR Pyrazoles.
Structure, 23:1470-1481, 2015

PubMed Abstract: CBR hydroxamidines are small-molecule inhibitors of bacterial RNA polymerase (RNAP) discovered through high-throughput screening of synthetic-compound libraries. CBR pyrazoles are structurally related RNAP inhibitors discovered through scaffold hopping from CBR hydroxamidines. CBR hydroxamidines and pyrazoles selectively inhibit Gram-negative bacterial RNAP and exhibit selective antibacterial activity against Gram-negative bacteria. Here, we report crystal structures of the prototype CBR hydroxamidine, CBR703, and a CBR pyrazole in complex with E. coli RNAP holoenzyme. In addition, we define the full resistance determinant for CBR703, show that the binding site and resistance determinant for CBR703 do not overlap the binding sites and resistance determinants of other characterized RNAP inhibitors, show that CBR703 exhibits no or minimal cross-resistance with other characterized RNAP inhibitors, and show that co-administration of CBR703 with other RNAP inhibitors results in additive antibacterial activities. The results set the stage for structure-based optimization of CBR inhibitors as antibacterial drugs.

PubMed: 26190576
DOI: 10.1016/j.str.2015.06.009

実験手法

X-RAY DIFFRACTION (3.993 Å)