4NW7

PDE4 catalytic domain

4NW7 の概要

• エントリーDOI: 10.2210/pdb4nw7/pdb
• 分子名称: cAMP-specific 3',5'-cyclic phosphodiesterase 4B, ZINC ION, MAGNESIUM ION, ... (7 entities in total)
• 機能のキーワード: phosphodiesterase, pde4, catalytic, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 43679.10

構造登録者

Fox III, D.,Edwards, T.E. (登録日: 2013-12-05, 公開日: 2014-10-15, 最終更新日: 2024-02-28)

主引用文献

Hagen, T.J.,Mo, X.,Burgin, A.B.,Fox, D.,Zhang, Z.,Gurney, M.E.
Discovery of triazines as selective PDE4B versus PDE4D inhibitors.
Bioorg.Med.Chem.Lett., 24:4031-4034, 2014

PubMed Abstract: In this study we report a series of triazine derivatives that are potent inhibitors of PDE4B. We also provide a series of structure activity relationships that demonstrate the triazine core can be used to generate subtype selective inhibitors of PDE4B versus PDE4D. A high resolution co-crystal structure shows that the inhibitors interact with a C-terminal regulatory helix (CR3) locking the enzyme in an inactive 'closed' conformation. The results show that the compounds interact with both catalytic domain and CR3 residues. This provides the first structure-based approach to engineer PDE4B-selective inhibitors.

PubMed: 24998378
DOI: 10.1016/j.bmcl.2014.06.002

実験手法

X-RAY DIFFRACTION (2.15 Å)