CBR antimicrobials alter coupling between the bridge helix and the β subunit in RNA polymerase.
CBR antimicrobials alter coupling between the bridge helix and the β subunit in RNA polymerase.
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DOI：
10.1038/ncomms4408
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发表时间：
2014-03-06
影响因子：
16.6
通讯作者：
Belogurov, Georgiy A.
中科院分区：
文献类型：
--
作者：
Malinen, Anssi M.;NandyMazumdar, Monali;Turtola, Matti;Malmi, Henri;Grocholski, Thadee;Artsimovitch, Irina;Belogurov, Georgiy A.
Bacterial RNA polymerase (RNAP) is a validated target for antibacterial drugs. CBR703 series antimicrobials allosterically inhibit transcription by binding to a conserved α helix (β′ bridge helix, BH) that interconnects the two largest RNAP subunits. Here we show that disruption of the BH-β subunit contacts by amino-acid substitutions invariably results in accelerated catalysis, slowed-down forward translocation and insensitivity to regulatory pauses. CBR703 partially reverses these effects in CBR-resistant RNAPs while inhibiting catalysis and promoting pausing in CBR-sensitive RNAPs. The differential response of variant RNAPs to CBR703 suggests that the inhibitor binds in a cavity walled by the BH, the β′ F-loop and the β fork loop. Collectively, our data are consistent with a model in which the β subunit fine tunes RNAP elongation activities by altering the BH conformation, whereas CBRs deregulate transcription by increasing coupling between the BH and the β subunit. Bacterial RNA polymerase (RNAP) is crucial for cellular gene expression and a validated target for antimicrobial drugs. Here, Malinen et al. explore the effects of the CBR class of RNAP inhibitors on the E. coli RNAP transcription cycle and provide detailed mechanistic insight into their antibacterial action.
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影响因子：
5.6
作者：
JONES, G;WILLETT, P;GLEN, RC
通讯作者：
GLEN, RC
影响因子：
64.5
作者：
Artsimovitch, I;Landick, R
通讯作者：
Landick, R
影响因子：
11.4
作者：
Bochkareva, Aleksandra;Yuzenkova, Yulia;Tadigotla, Vasisht R.;Zenkin, Nikolay
通讯作者：
Zenkin, Nikolay
影响因子：
3
作者：
BROOKS, BR;BRUCCOLERI, RE;KARPLUS, M
通讯作者：
KARPLUS, M
DOI：
10.1073/pnas.82.14.4663
发表时间：
1985-01-01
影响因子：
11.1
作者：
LANDICK, R;CAREY, J;YANOFSKY, C
通讯作者：
YANOFSKY, C