4OTY

Crystal structure of lumiracoxib bound to the apo-mouse-cyclooxygenase-2

「4LLZ」から置き換えられました

4OTY の概要

• エントリーDOI: 10.2210/pdb4oty/pdb
• 分子名称: Prostaglandin G/H synthase 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: protein-drug complex, oxidoreductase, nsaids, heme, glycosylation, monotopic membrane protein, drug complex, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• 由来する生物種: Mus musculus (mouse)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 137278.87

構造登録者

Xu, S.,Windsor, M.A.,Banerjee, S.,Marnett, L.J. (登録日: 2014-02-14, 公開日: 2014-02-26, 最終更新日: 2024-11-27)

主引用文献

Windsor, M.A.,Valk, P.L.,Xu, S.,Banerjee, S.,Marnett, L.J.
Exploring the molecular determinants of substrate-selective inhibition of cyclooxygenase-2 by lumiracoxib.
Bioorg.Med.Chem.Lett., 23:5860-5864, 2013

PubMed Abstract: Lumiracoxib is a substrate-selective inhibitor of endocannabinoid oxygenation by cyclooxygenase-2 (COX-2). We assayed a series of lumiracoxib derivatives to identify the structural determinants of substrate-selective inhibition. The hydrogen-bonding potential of the substituents at the ortho positions of the aniline ring dictated the potency and substrate selectivity of the inhibitors. The presence of a 5'-methyl group on the phenylacetic acid ring increased the potency of molecules with a single ortho substituent. Des-fluorolumiracoxib (2) was the most potent and selective inhibitor of endocannabinoid oxygenation. The positioning of critical substituents in the binding site was identified from a 2.35Å crystal structure of lumiracoxib bound to COX-2.

PubMed: 24060487
DOI: 10.1016/j.bmcl.2013.08.097

実験手法

X-RAY DIFFRACTION (2.354 Å)