4JIB

Crystal structure of of PDE2-inhibitor complex

4JIB の概要

• エントリーDOI: 10.2210/pdb4jib/pdb
• 関連するPDBエントリー: 3ITM
• 分子名称: cGMP-dependent 3',5'-cyclic phosphodiesterase, ZINC ION, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Isoform PDE2A3: Cell membrane ; Lipid-anchor . Isoform PDE2A2: Mitochondrion matrix . Isoform PDE2A1: Cytoplasm . Isoform 5: Mitochondrion : O00408
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 162941.29

構造登録者

Pandit, J. (登録日: 2013-03-05, 公開日: 2013-05-01, 最終更新日: 2024-02-28)

主引用文献

Plummer, M.S.,Cornicelli, J.,Roark, H.,Skalitzky, D.J.,Stankovic, C.J.,Bove, S.,Pandit, J.,Goodman, A.,Hicks, J.,Shahripour, A.,Beidler, D.,Lu, X.K.,Sanchez, B.,Whitehead, C.,Sarver, R.,Braden, T.,Gowan, R.,Shen, X.Q.,Welch, K.,Ogden, A.,Sadagopan, N.,Baum, H.,Miller, H.,Banotai, C.,Spessard, C.,Lightle, S.
Discovery of potent, selective, bioavailable phosphodiesterase 2 (PDE2) inhibitors active in an osteoarthritis pain model, Part I: Transformation of selective pyrazolodiazepinone phosphodiesterase 4 (PDE4) inhibitors into selective PDE2 inhibitors.
Bioorg.Med.Chem.Lett., 23:3438-3442, 2013

PubMed Abstract: We identified potent, selective PDE2 inhibitors by optimizing residual PDE2 activity in a series of PDE4 inhibitors, while simultaneously minimizing PDE4 activity. These newly designed PDE2 inhibitors bind to the PDE2 enzyme in a cGMP-like mode in contrast to the cAMP-like binding mode found in PDE4. Structure activity relationship studies coupled with an inhibitor bound crystal structure in the active site of the catalytic domain of PDE2 identified structural features required to minimize PDE4 inhibition while simultaneously maximizing PDE2 inhibition.

PubMed: 23582272
DOI: 10.1016/j.bmcl.2013.03.072

実験手法

X-RAY DIFFRACTION (1.72 Å)