Flavonoids play beneficial roles in various human diseases. In this study, a flavonoid library was employed to probe inhibitors of d-glycero-β-d-manno-heptose-1-phosphate adenylyltransferase from Burkholderia pseudomallei (BpHldC) and two flavonoids, epigallocatechin gallate (EGCG) and myricetin, have been discovered. BpHldC is one of the essential enzymes in the ADP-l-glycero-β-d-manno-heptose biosynthesis pathway constructing lipopolysaccharide of B. pseudomallei. Enzyme kinetics study showed that two flavonoids work through different mechanisms to block the catalytic activity of BpHldC. Among them, a docking study of EGCG was performed and the binding mode could explain its competitive inhibitory mode for both ATP and βG1P. Analyses with EGCG homologs could reveal the important functional moieties, too. This study is the first example of uncovering the inhibitory activity of flavonoids against the ADP-l-glycero-β-d-manno-heptose biosynthesis pathway and especially targeting HldC. Since there are no therapeutic agents and vaccines available against melioidosis, EGCG and myricetin can be used as templates to develop antibiotics over B. pseudomallei.

中文翻译：

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没食子儿茶素没食子酸酯和杨梅素抑制假苹果伯克霍尔德氏菌的d-甘油-β-d-甘露庚糖1-磷酸腺苷基转移酶

类黄酮在各种人类疾病中发挥有益作用。在这项研究中，使用了类黄酮文库来探究拟南芥伯克霍尔德氏菌（BpHldC）的d-甘油-β-d-甘露庚糖-1-磷酸腺苷酸转移酶的抑制剂，并且发现了两个类黄酮，表没食子儿茶素没食子酸酯（EGCG）和杨梅素。BpHldC是构建假疟原虫脂多糖的ADP-1-甘油-β-d-甘露聚糖-庚糖生物合成途径中的必需酶之一。酶动力学研究表明，两种类黄酮通过不同的机理阻断BpHldC的催化活性。其中，进行了EGCG的对接研究，结合模式可以解释其对ATP和βG1P的竞争性抑制模式。用EGCG同源物进行的分析也可以揭示重要的功能部分。该研究是揭示类黄酮对ADP-1-甘油-β-d-甘露聚糖-庚糖生物合成途径特别是针对HldC的抑制活性的第一个实例。由于尚无抗类胡萝卜素的治疗剂和疫苗，因此可以将EGCG和杨梅素用作模板，以开发出比假苹果芽孢杆菌更强的抗生素。