5WYS

luciferase with inhibitor 3i

Summary for 5WYS

• Entry DOI: 10.2210/pdb5wys/pdb
• Descriptor: Luciferin 4-monooxygenase, 5-[(3R)-3-(4-boranylphenyl)-3-oxidanyl-propyl]-2-oxidanyl-benzoic acid (2 entities in total)
• Functional Keywords: luciferase, inhibitor, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• Biological source: Photinus pyralis (Common eastern firefly)
• Cellular location: Peroxisome : P08659
• Total number of polymer chains: 1
• Total formula weight: 61103.07

Authors

Gu, L.,Su, J.,Wang, F. (deposition date: 2017-01-15, release date: 2017-12-27, Last modification date: 2024-03-20)

Primary citation

Zhang, H.,Su, J.,Lin, Y.,Bai, H.,Liu, J.,Chen, H.,Du, L.,Gu, L.,Li, M.
Inhibiting Firefly Bioluminescence by Chalcones
Anal. Chem., 89:6099-6105, 2017

PubMed Abstract: Chalcone refers to an aromatic ketone and an enone that constitutes the central core for various important biological compounds in drug discovery. Moreover, the firefly luciferase (Fluc) as the bioluminescent reporter has been widely used in life science research and high-throughput screening (HTS). However, Fluc might suffer from direct inhibition by HTS compounds resulting in the occurrence of "false positives." In the current research, we discovered a series of chalcone compounds as Fluc inhibitors with favorable potency both in vitro and in vivo. Moreover, our compound 3i showed remarkable systemic inhibition in transgenic mice. Both enzymatic kinetics study and cocrystal structure demonstrated that compound 3i is competitive for substrate aminoluciferin, while noncompetitive for ATP. Besides, compound 3i exhibited excellent selectivity as a promising quenching agent in a simulated dual-luciferase reporter assay. We believed that our research would contribute to improving scientists' awareness of the Fluc inhibitors, pay attention to the bias results, and even expand the utilization of bioluminescence in life science research.

PubMed: 28492074
DOI: 10.1021/acs.analchem.7b00813

Experimental method

X-RAY DIFFRACTION (2.999 Å)