4E5D

2.2A resolution structure of a firefly luciferase-benzothiazole inhibitor complex

4E5D の概要

• エントリーDOI: 10.2210/pdb4e5d/pdb
• 分子名称: Luciferin 4-monooxygenase, 2-(2-fluorophenyl)-6-methoxy-1,3-benzothiazole (3 entities in total)
• 機能のキーワード: oxidoreductase, monooxygenase, photoprotein, luminescence, profiling, pubchem, luciferase, quantitative high-throughput screening, qhts, firefly luciferase, reporter-gene assays, adenylate forming enzymes, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• 由来する生物種: Photinus pyralis (North American firefly)
• 細胞内の位置: Peroxisome : P08659
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 61078.25

構造登録者

Lovell, S.,Battaile, K.P.,Throne, N.,Shen, M.,Auld, D.S.,Inglese, J. (登録日: 2012-03-14, 公開日: 2012-09-05, 最終更新日: 2023-09-13)

主引用文献

Thorne, N.,Shen, M.,Lea, W.A.,Simeonov, A.,Lovell, S.,Auld, D.S.,Inglese, J.
Firefly luciferase in chemical biology: a compendium of inhibitors, mechanistic evaluation of chemotypes, and suggested use as a reporter.
Chem.Biol., 19:1060-1072, 2012

PubMed Abstract: Firefly luciferase (FLuc) is frequently used as a reporter in high-throughput screening assays, owing to the exceptional sensitivity, dynamic range, and rapid measurement that bioluminescence affords. However, interaction of small molecules with FLuc has, to some extent, confounded its use in chemical biology and drug discovery. To identify and characterize chemotypes interacting with FLuc, we determined potency values for 360,864 compounds found in the NIH Molecular Libraries Small Molecule Repository, available in PubChem. FLuc inhibitory activity was observed for 12% of this library with discernible SAR. Characterization of 151 inhibitors demonstrated a variety of inhibition modes, including FLuc-catalyzed formation of multisubstrate adduct enzyme inhibitor complexes. As in some cell-based FLuc reporter assays, compounds acting as FLuc inhibitors yield paradoxical luminescence increases, thus data on compounds acquired from FLuc-dependent assays require careful analysis as described here.

PubMed: 22921073
DOI: 10.1016/j.chembiol.2012.07.015

実験手法

X-RAY DIFFRACTION (2.201 Å)