Illuminating Insights into Firefly Luciferase and Other Bioluminescent Reporters Used in Chemical Biology

Overview

Journal Chem Biol

Publisher Elsevier

Specialties Biochemistry
Biology
Chemistry

Date 2010 Jul 9

PMID 20609414

Citations 126

Authors

Natasha Thorne

James Inglese

Douglas S Auld

Affiliations

Soon will be listed here.

Abstract

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 counterintuitive 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 and stabilization can be complex, as illustrated by the compound PTC124, which is converted by FLuc in the presence of ATP to a high affinity multisubstrate adduct inhibitor, PTC124-AMP. The potential influence these findings can have on drug discovery efforts is provided here.

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