3JWR

Crystal structure of chimeric PDE5/PDE6 catalytic domain complexed with 3-isobutyl-1-methylxanthine (IBMX) and PDE6 gamma-subunit inhibitory peptide 70-87.

3JWR の概要

• エントリーDOI: 10.2210/pdb3jwr/pdb
• 関連するPDBエントリー: 3JWQ
• 分子名称: cGMP-specific 3',5'-cyclic phosphodiesterase catalytic domain, Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha chimera, Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma, ZINC ION, ... (6 entities in total)
• 機能のキーワード: mostly alpha, cgmp, hydrolase, polymorphism, sensory transduction, vision
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 82225.69

構造登録者

Barren, B.,Gakhar, L.,Muradov, H.,Boyd, K.K.,Ramaswamy, S.,Artemyev, N.O. (登録日: 2009-09-18, 公開日: 2009-10-13, 最終更新日: 2024-11-06)

主引用文献

Barren, B.,Gakhar, L.,Muradov, H.,Boyd, K.K.,Ramaswamy, S.,Artemyev, N.O.
Structural basis of phosphodiesterase 6 inhibition by the C-terminal region of the gamma-subunit
Embo J., 28:3613-3622, 2009

PubMed Abstract: The inhibitory interaction of phosphodiesterase-6 (PDE6) with its gamma-subunit (Pgamma) is pivotal in vertebrate phototransduction. Here, crystal structures of a chimaeric PDE5/PDE6 catalytic domain (PDE5/6cd) complexed with sildenafil or 3-isobutyl-1-methylxanthine and the Pgamma-inhibitory peptide Pgamma(70-87) have been determined at 2.9 and 3.0 A, respectively. These structures show the determinants and the mechanism of the PDE6 inhibition by Pgamma and suggest the conformational change of Pgamma on transducin activation. Two variable H- and M-loops of PDE5/6cd form a distinct interface that contributes to the Pgamma-binding site. This allows the Pgamma C-terminus to fit into the opening of the catalytic pocket, blocking cGMP access to the active site. Our analysis suggests that disruption of the H-M loop interface and Pgamma-binding site is a molecular cause of retinal degeneration in atrd3 mice. Comparison of the two PDE5/6cd structures shows an overlap between the sildenafil and Pgamma(70-87)-binding sites, thereby providing critical insights into the side effects of PDE5 inhibitors on vision.

PubMed: 19798052
DOI: 10.1038/emboj.2009.284

実験手法

X-RAY DIFFRACTION (2.994 Å)