2PW3

Structure of the PDE4D-cAMP complex

2PW3 の概要

• エントリーDOI: 10.2210/pdb2pw3/pdb
• 分子名称: cAMP-specific 3',5'-cyclic phosphodiesterase 4D, ZINC ION, ADENOSINE-3',5'-CYCLIC-MONOPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: pde4-camp complex, substrate specificity, crystal structure., 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: 2
• 化学式量合計: 76200.71

構造登録者

Wang, H.,Robinson, H.,Ke, H. (登録日: 2007-05-10, 公開日: 2007-10-23, 最終更新日: 2024-04-03)

主引用文献

Wang, H.,Robinson, H.,Ke, H.
The molecular basis for different recognition of substrates by phosphodiesterase families 4 and 10.
J.Mol.Biol., 371:302-307, 2007

PubMed Abstract: Phosphodiesterases (PDEs) are key enzymes that control the cellular concentrations of the second messengers cAMP and cGMP. The mechanism for selective recognition of substrates cAMP and cGMP by individual PDE families remains a puzzle. To understand the mechanism for substrate recognition by PDE enzymes, the crystal structure of the catalytic domain of an inactive D201N mutant of PDE4D2 in complex with substrate cAMP has been determined at 1.56 A resolution. The structure shows that Gln369 forms only one hydrogen bond with the adenine of cAMP. This finding provides experimental evidence against the hypothesis of two hydrogen bonds between the invariant glutamine and the substrate cAMP in PDE4, and thus suggests that the widely circulated "glutamine switch" model is unlikely the mechanism for substrate recognition by PDEs. A structure comparison between PDE4D2-cAMP and PDE10A2-cAMP reveals an anti configuration of cAMP in PDE4D2 but syn in PDE10A2, in addition to different contact patterns of cAMP in these two structures. These observations imply that individual PDE families have their characteristic mechanisms for substrate recognition.

PubMed: 17582435
DOI: 10.1016/j.jmb.2007.05.060

実験手法

X-RAY DIFFRACTION (1.56 Å)