5KIR

The Structure of Vioxx Bound to Human COX-2

5KIR の概要

• エントリーDOI: 10.2210/pdb5kir/pdb
• 分子名称: Prostaglandin G/H synthase 2, alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, Rofecoxib, ... (9 entities in total)
• 機能のキーワード: cyclooxyrgenase, vioxx, rofecoxib, cox, oxidoreductase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 131003.98

構造登録者

Orlando, B.J.,Malkowski, M.G. (登録日: 2016-06-16, 公開日: 2016-09-28, 最終更新日: 2024-11-13)

主引用文献

Orlando, B.J.,Malkowski, M.G.
Crystal structure of rofecoxib bound to human cyclooxygenase-2.
Acta Crystallogr.,Sect.F, 72:772-776, 2016

PubMed Abstract: Rofecoxib (Vioxx) was one of the first selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) to be approved for use in humans. Within five years after its release to the public, Vioxx was withdrawn from the market owing to the adverse cardiovascular effects of the drug. Despite the widespread knowledge of the development and withdrawal of Vioxx, relatively little is known at the molecular level about how the inhibitor binds to COX-2. Vioxx is unique in that the inhibitor contains a methyl sulfone moiety in place of the sulfonamide moiety found in other coxibs such as celecoxib and valdecoxib. Here, new crystallization conditions were identified that allowed the structural determination of human COX-2 in complex with Vioxx and the structure was subsequently determined to 2.7 Å resolution. The crystal structure provides the first atomic level details of the binding of Vioxx to COX-2. As anticipated, Vioxx binds with its methyl sulfone moiety located in the side pocket of the cyclooxygenase channel, providing support for the isoform selectivity of this drug.

PubMed: 27710942
DOI: 10.1107/S2053230X16014230

実験手法

X-RAY DIFFRACTION (2.697 Å)