3O0J

PDE4B In complex with ligand an2898

3O0J の概要

• エントリーDOI: 10.2210/pdb3o0j/pdb
• 分子名称: cAMP-specific 3',5'-cyclic phosphodiesterase 4B, ZINC ION, MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: phosphodiesterase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 38548.01

構造登録者

Alley, M.R.K.,Zhou, Y. (登録日: 2010-07-19, 公開日: 2011-08-10, 最終更新日: 2024-02-21)

主引用文献

Freund, Y.R.,Akama, T.,Alley, M.R.,Antunes, J.,Dong, C.,Jarnagin, K.,Kimura, R.,Nieman, J.A.,Maples, K.R.,Plattner, J.J.,Rock, F.,Sharma, R.,Singh, R.,Sanders, V.,Zhou, Y.
Boron-based phosphodiesterase inhibitors show novel binding of boron to PDE4 bimetal center.
Febs Lett., 586:3410-3414, 2012

PubMed Abstract: We have used boron-based molecules to create novel, competitive, reversible inhibitors of phosphodiesterase 4 (PDE4). The co-crystal structure reveals a binding configuration which is unique compared to classical catechol PDE4 inhibitors, with boron binding to the activated water in the bimetal center. These phenoxybenzoxaboroles can be optimized to generate submicromolar potency enzyme inhibitors, which inhibit TNF-α, IL-2, IFN-γ, IL-5 and IL-10 activities in vitro and show safety and efficacy for topical treatment of human psoriasis. They provide a valuable new route for creating novel potent anti-PDE4 inhibitors.

PubMed: 22841723
DOI: 10.1016/j.febslet.2012.07.058

実験手法

X-RAY DIFFRACTION (1.95 Å)