1Q9M

Three dimensional structures of PDE4D in complex with roliprams and implication on inhibitor selectivity

「1OYM」から置き換えられました

1Q9M の概要

• エントリーDOI: 10.2210/pdb1q9m/pdb
• 分子名称: cAMP-specific phosphodiesterase PDE4D2, ZINC ION, ROLIPRAM, ... (4 entities in total)
• 機能のキーワード: pde, rolipram, specific inhibitor, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm (By similarity): Q08499
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 167203.74

構造登録者

Huai, Q.,Wang, H.,Sun, Y.,Kim, H.Y.,Liu, Y.,Ke, H. (登録日: 2003-08-25, 公開日: 2003-09-02, 最終更新日: 2024-04-03)

主引用文献

Huai, Q.,Wang, H.,Sun, Y.,Kim, H.Y.,Liu, Y.,Ke, H.
Three dimensional structures of PDE4D in complex with roliprams and implication on inhibitor selectivity
Structure, 11:865-873, 2003

PubMed Abstract: Selective inhibitors against the 11 families of cyclic nucleotide phosphodiesterases (PDEs) are used to treat various human diseases. How the inhibitors selectively bind the conserved PDE catalytic domains is unknown. The crystal structures of the PDE4D2 catalytic domain in complex with (R)- or (R,S)-rolipram suggest that inhibitor selectivity is determined by the chemical nature of amino acids and subtle conformational changes of the binding pockets. The conformational states of Gln369 in PDE4D2 may play a key role in inhibitor recognition. The corresponding Y329S mutation in PDE7 may lead to loss of the hydrogen bonds between rolipram and Gln369 and is thus a possible reason explaining PDE7's insensitivity to rolipram inhibition. Docking of the PDE5 inhibitor sildenafil into the PDE4 catalytic pocket further helps understand inhibitor selectivity.

PubMed: 12842049
DOI: 10.1016/S0969-2126(03)00123-0

実験手法

X-RAY DIFFRACTION (2.3 Å)