Antibacterial peptide microcin J25 inhibits transcription by binding within and obstructing the RNA polymerase secondary channel
Antibacterial peptide microcin J25 inhibits transcription by binding within and obstructing the RNA polymerase secondary channel
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DOI：
10.1016/j.molcel.2004.06.010
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发表时间：
2004-06-18
期刊：
影响因子：
16
通讯作者：
Ebright, RH
中科院分区：
文献类型：
--
作者：
Mukhopadhyay, J;Sineva, E;Ebright, RH
抗菌肽microcin J25（MccJ25）抑制细菌RNA聚合酶（RNAP）的转录。生化结果表明，转录抑制发生在NTP摄取或NTP结合RNAP的水平。遗传结果表明，转录的抑制需要广泛的决定簇，包括超过50个氨基酸残基，在RNAP二级通道（也称为“NTP摄取通道”或“孔”）。生物物理结果表明，转录的抑制涉及RNAP二级通道内MccJ25的结合。分子模拟表明，RNAP二级通道内MccJ25的结合阻碍了RNAP二级通道。我们的结论是MccJ25通过结合并阻断RNAP二级通道来抑制转录，其作用实质上就像“瓶塞”。RNAP二级通道的阻塞代表了药物发现的一个有吸引力的目标。
The antibacterial peptide microcin J25 (MccJ25) inhibits transcription by bacterial RNA polymerase (RNAP). Biochemical results indicate that inhibition of transcription occurs at the level of NTP uptake or NTP binding by RNAP. Genetic results indicate that inhibition of transcription requires an extensive determinant, comprising more than 50 amino acid residues, within the RNAP secondary channel (also known as the "NTP-uptake channel" or "pore"). Biophysical results indicate that inhibition of transcription involves binding of MccJ25 within the RNAP secondary channel. Molecular modeling indicates that binding of MccJ25 within the RNAP secondary channel obstructs the RNAP secondary channel. We conclude that MccJ25 inhibits transcription by binding within and obstructing the RNAP secondary channel-acting essentially as a "cork in a bottle." Obstruction of the RNAP secondary channel represents an attractive target for drug discovery.