3DYS

human phosphodiestrase-5'GMP complex (EP), produced by soaking with 20mM cGMP+20 mM MnCl2+20 mM MgCl2 for 2 hours, and flash-cooled to liquid nitrogen temperature when substrate was still abudant.

3DYS の概要

• エントリーDOI: 10.2210/pdb3dys/pdb
• 関連するPDBエントリー: 3DY8 3DYL 3DYN 3DYQ
• 分子名称: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A, MANGANESE (II) ION, MAGNESIUM ION, ... (7 entities in total)
• 機能のキーワード: phosphodiestrase, enzyme mechanism, cgmp, hydrolase, manganese, metal-binding, phosphoprotein
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Isoform PDE9A1: Cell projection, ruffle membrane. Isoform PDE9A2: Cell projection, ruffle membrane. Isoform PDE9A3: Cytoplasm. Isoform PDE9A17: Cytoplasm: O76083
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 78625.70

構造登録者

Liu, S.,Mansour, M.N.,Dillman, K.,Perez, J.,Danley, D.,Menniti, F. (登録日: 2008-07-28, 公開日: 2008-09-16, 最終更新日: 2024-02-21)

主引用文献

Liu, S.,Mansour, M.N.,Dillman, K.S.,Perez, J.R.,Danley, D.E.,Aeed, P.A.,Simons, S.P.,Lemotte, P.K.,Menniti, F.S.
Structural basis for the catalytic mechanism of human phosphodiesterase 9.
Proc.Natl.Acad.Sci.Usa, 105:13309-13314, 2008

PubMed Abstract: The phosphodiesterases (PDEs) are metal ion-dependent enzymes that regulate cellular signaling by metabolic inactivation of the ubiquitous second messengers cAMP and cGMP. In this role, the PDEs are involved in many biological and metabolic processes and are proven targets of successful drugs for the treatments of a wide range of diseases. However, because of the rapidity of the hydrolysis reaction, an experimental knowledge of the enzymatic mechanisms of the PDEs at the atomic level is still lacking. Here, we report the structures of reaction intermediates accumulated at the reaction steady state in PDE9/crystal and preserved by freeze-trapping. These structures reveal the catalytic process of a PDE and explain the substrate specificity of PDE9 in an actual reaction and the cation requirements of PDEs in general.

PubMed: 18757755
DOI: 10.1073/pnas.0708850105

実験手法

X-RAY DIFFRACTION (2.3 Å)