1ZKN

Structure of PDE4D2-IBMX

「1RKO」から置き換えられました

1ZKN の概要

• エントリーDOI: 10.2210/pdb1zkn/pdb
• 関連するPDBエントリー: 1RKO
• 分子名称: cAMP-specific 3',5'-cyclic phosphodiesterase 4D, ZINC ION, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: protein-inhibitor complex, inhibitor selectivity, 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: 155274.74

構造登録者

Huai, Q.,Liu, Y.,Francis, S.H.,Corbin, J.D.,Ke, H. (登録日: 2005-05-03, 公開日: 2005-05-17, 最終更新日: 2024-04-03)

主引用文献

Huai, Q.,Liu, Y.,Francis, S.H.,Corbin, J.D.,Ke, H.
Crystal Structures of Phosphodiesterases 4 and 5 in Complex with Inhibitor 3-Isobutyl-1-Methylxanthine Suggest a Conformation Determinant of Inhibitor Selectivity
J.Biol.Chem., 279:13095-13101, 2004

PubMed Abstract: Cyclic nucleotide phosphodiesterases (PDEs) are a superfamily of enzymes controlling cellular concentrations of the second messengers cAMP and cGMP. Crystal structures of the catalytic domains of cGMP-specific PDE5A1 and cAMP-specific PDE4D2 in complex with the nonselective inhibitor 3-isobutyl-1-methylxanthine have been determined at medium resolution. The catalytic domain of PDE5A1 has the same topological folding as that of PDE4D2, but three regions show different tertiary structures, including residues 79-113, 208-224 (H-loop), and 341-364 (M-loop) in PDE4D2 or 535-566, 661-676, and 787-812 in PDE5A1, respectively. Because H- and M-loops are involved in binding of the selective inhibitors, the different conformations of the loops, thus the distinct shapes of the active sites, will be a determinant of inhibitor selectivity in PDEs. IBMX binds to a subpocket that comprises key residues Ile-336, Phe-340, Gln-369, and Phe-372 of PDE4D2 or Val-782, Phe-786, Gln-817, and Phe-820 of PDE5A1. This subpocket may be a common site for binding nonselective inhibitors of PDEs.

PubMed: 14668322
DOI: 10.1074/jbc.M311556200

実験手法

X-RAY DIFFRACTION (2.1 Å)