3IBJ

X-ray structure of PDE2A

3IBJ の概要

• エントリーDOI: 10.2210/pdb3ibj/pdb
• 分子名称: cGMP-dependent 3',5'-cyclic phosphodiesterase, ZINC ION, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: phosphodiesterase, pde2a, gaf-domains, allosteric regulation, cgmp, hydrolase, membrane
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Peripheral membrane protein (Potential): O00408
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 158083.99

構造登録者

Pandit, J. (登録日: 2009-07-16, 公開日: 2009-10-27, 最終更新日: 2023-09-06)

主引用文献

Pandit, J.,Forman, M.D.,Fennell, K.F.,Dillman, K.S.,Menniti, F.S.
Mechanism for the allosteric regulation of phosphodiesterase 2A deduced from the X-ray structure of a near full-length construct.
Proc.Natl.Acad.Sci.USA, 106:18225-18230, 2009

PubMed Abstract: We report the X-ray crystal structure of a phosphodiesterase (PDE) that includes both catalytic and regulatory domains. PDE2A (215-900) crystallized as a dimer in which each subunit had an extended organization of regulatory GAF-A and GAF-B and catalytic domains connected by long alpha-helices. The subunits cross at the GAF-B/catalytic domain linker, and each side of the dimer contains in series the GAF-A and GAF-B of one subunit and the catalytic domain of the other subunit. A dimer interface extends over the entire length of the molecule. The substrate binding pocket of each catalytic domain is occluded by the H-loop. We deduced from comparisons with structures of isolated, ligand-bound catalytic subunits that the H-loop swings out to allow substrate access. However, in dimeric PDE2A (215-900), the H-loops of the two catalytic subunits pack against each other at the dimer interface, necessitating movement of the catalytic subunits to allow for H-loop movement. Comparison of the unliganded GAF-B of PDE2A (215-900) with previous structures of isolated, cGMP-bound GAF domains indicates that cGMP binding induces a significant shift in the GAF-B/catalytic domain linker. We propose that cGMP binding to GAF-B causes movement, through this linker region, of the catalytic domains, such that the H-loops no longer pack at the dimer interface and are, instead, free to swing out to allow substrate access. This increase in substrate access is proposed as the basis for PDE2A activation by cGMP and may be a general mechanism for regulation of all PDEs.

PubMed: 19828435
DOI: 10.1073/pnas.0907635106

実験手法

X-RAY DIFFRACTION (3.02 Å)