Myricetin inhibits Escherichia coli DnaB helicase but not primase
Myricetin inhibits Escherichia coli DnaB helicase but not primase
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DOI：
10.1016/j.bmc.2007.07.057
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发表时间：
2007-11-15
影响因子：
3.5
通讯作者：
Hinrichs, Steven H.
中科院分区：
文献类型：
--
作者：
Griep, Mark A.;Blood, Sheldon;Hinrichs, Steven H.
引物酶和 DnaB 解旋酶在 DNA 复制起始和延伸过程中发挥着核心作用。这两种酶都是药物靶点，因为它们是必需的，在细菌基因组中持续存在，并且与真核生物具有不同的序列。杨梅素是植物中普遍存在的天然产物，已知可抑制多种 DNA 聚合酶、RNA 聚合酶、逆转录酶和端粒酶，此外还能抑制激酶和解旋酶。我们已经证明，杨梅素根据非竞争性行为主导的机制抑制大肠杆菌 DnaB 解旋酶，K-i 为 10.0 +/- 0.5 μM。在生理 ATP 浓度下，杨梅素抑制大肠杆菌 DnaB 解旋酶，50% 最大抑制浓度 (IC50) 为 11.3 +/- 1.6 μM。相比之下，杨梅素 对大肠杆菌引物酶的抑制作用比 DnaB 解旋酶至少弱 60 倍，并且比任何其他聚合酶都弱得多。 (C) 2007 Elsevier Ltd. 保留所有权利。
Primase and DnaB helicase play central roles during DNA replication initiation and elongation. Both enzymes are drug targets because they are essential, persistent among bacterial genomes, and have different sequences than their eukaryotic equivalents. Myricetin is a ubiquitous natural product in plants that is known to inhibit a variety of DNA polymerases, RNA polymerases, reverse transcriptases, and telomerases in addition being able to inhibit kinases and helicases. We have shown that myricetin inhibits Escherichia coli DnaB helicase according to a mechanism dominated by noncompetitive behavior with a K-i of 10.0 +/- 0.5 mu M. At physiological ATP concentration, myricetin inhibits E. coli DnaB helicase with an inhibitory concentration at 50% maximal (IC50) of 11.3 +/- 1.6 mu M. In contrast, myricetin inhibited E coli primase at least 60-fold weaker than DnaB helicase and far weaker than any other polymerase. (C) 2007 Elsevier Ltd. All rights reserved.