Illuminating insights into firefly luciferase and other bioluminescent reporters used in chemical biology.
Illuminating insights into firefly luciferase and other bioluminescent reporters used in chemical biology.
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DOI：
10.1016/j.chembiol.2010.05.012
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发表时间：
2010-06-25
影响因子：
--
通讯作者：
Auld DS
中科院分区：
文献类型：
--
作者：
Thorne N;Inglese J;Auld DS
了解荧光素酶的酶学和调节荧光素酶活性的化合物的结构可以用来改进基于发光的检测的设计。本文综述了这些流行的荧光素酶，重点介绍了Photinus pyralis （FLuc）中常用的萤火虫荧光素酶。大规模的化学谱研究已经确定了多种抑制FLuc的支架。在一些基于细胞的分析中，这些抑制剂可以以一种反直觉的方式起作用——导致发光信号的增益。虽然以前归因于转录激活，但FLuc的细胞内稳定是这一观察的主要机制。FLuc抑制/稳定可能是复杂的，如化合物PTC124所示，它在ATP存在下被FLuc转化为高亲和力的多底物加合物抑制剂PTC124- amp。这些发现可能对药物发现工作产生的潜在影响在这里提供。
Understanding luciferase enzymology and the structure of compounds that modulate luciferase activity can be used to improve the design of luminescence-based assays. This review provides an overview of these popular reporters with an emphasis on the commonly used firefly luciferase from Photinus pyralis (FLuc). Large-scale chemical profile studies have identified a variety of scaffolds that inhibit FLuc. In some cell-based assays these inhibitors can act in a counter-intuitive way –leading to a gain in luminescent signal. Although formerly attributed to transcriptional activation, intracellular stabilization of FLuc is the primary mechanism underlying this observation. FLuc inhibition/stabilization can be complex, as illustrated by the compound PTC124, which is converted by FLuc in the presence of ATP to a high affinity multi-substrate-adduct inhibitor, PTC124-AMP. The potential influence these findings can have on drug discovery efforts is provided here.
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影响因子：
5.4
作者：
Fontes, Rui;Fernandes, Diogo;da Silva, Joaquim C. G. Esteves
通讯作者：
da Silva, Joaquim C. G. Esteves
影响因子：
1.8
作者：
Davis, R. Eric;Zhang, Ya-Qin;Auld, Douglas S.
通讯作者：
Auld, Douglas S.
影响因子：
2.6
作者：
Ghiradella, H;Schmidt, JT
通讯作者：
Schmidt, JT
影响因子：
4
作者：
Auld, Douglas S.;Thorne, Natasha;Nguyen, Dac-Trung;Inglese, James
通讯作者：
Inglese, James
影响因子：
4
作者：
Fan, Frank;Binkowski, Brock F.;Wood, Keith V.
通讯作者：
Wood, Keith V.