Structural mechanism for rifampicin inhibition of bacterial RNA polymerase
Structural mechanism for rifampicin inhibition of bacterial RNA polymerase
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DOI：
10.1016/s0092-8674(01)00286-0
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发表时间：
2001-03-23
期刊：
影响因子：
64.5
通讯作者：
Darst, SA
中科院分区：
文献类型：
--
作者：
Campbell, EA;Korzheva, N;Darst, SA
利福平 (Rif) 是针对细菌病原体最有效、最广谱的抗生素之一，并且由于其抑制细菌 RNA 聚合酶 (RNAP) 而成为抗结核治疗的关键组成部分。我们确定了与 Rif 复合的栖热菌核心 RNAP 的晶体结构。该抑制剂结合在 DNA/RNA 通道深处 RNAP β 亚基的口袋中，但距离活性位点超过 12 埃。该结构与生化结果相结合，解释了 Rif 对 RNAP 功能的影响，并表明当转录物长度变为 2 至 3 nt 时，抑制剂通过直接阻断 RNA 延伸路径发挥作用。
Rifampicin (Rif) is one of the most potent and broad spectrum antibiotics against bacterial pathogens and is a key component of anti-tuberculosis therapy, stemming from its inhibition of the bacterial RNA polymerase (RNAP). We determined the crystal structure of Thermus aquaticus core RNAP complexed with Rif. The inhibitor binds in a pocket of the RNAP beta subunit deep within the DNA/RNA channel, but more than 12 Angstrom away from the active site. The structure, combined with biochemical results, explains the effects of Rif on RNAP function and indicates that the inhibitor acts by directly blocking the path of the elongating RNA when the transcript becomes 2 to 3 nt in length.