1TBF

Catalytic Domain Of Human Phosphodiesterase 5A in Complex with Sildenafil

1TBF の概要

• エントリーDOI: 10.2210/pdb1tbf/pdb
• 関連するPDBエントリー: 1T9R 1T9S 1TAZ 1TB5 1TB7 1TBB
• 分子名称: cGMP-specific 3',5'-cyclic phosphodiesterase, ZINC ION, MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: pde5a, hydrolase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 40568.17

構造登録者

Zhang, K.Y.J.,Card, G.L.,Suzuki, Y.,Artis, D.R.,Fong, D.,Gillette, S.,Hsieh, D.,Neiman, J.,West, B.L.,Zhang, C.,Milburn, M.V.,Kim, S.-H.,Schlessinger, J.,Bollag, G. (登録日: 2004-05-20, 公開日: 2004-08-03, 最終更新日: 2023-08-23)

主引用文献

Zhang, K.Y.J.,Card, G.L.,Suzuki, Y.,Artis, D.R.,Fong, D.,Gillette, S.,Hsieh, D.,Neiman, J.,West, B.L.,Zhang, C.,Milburn, M.V.,Kim, S.-H.,Schlessinger, J.,Bollag, G.
A Glutamine Switch Mechanism for Nucleotide Selectivity by Phosphodiesterases
Mol.Cell, 15:279-286, 2004

PubMed Abstract: Phosphodiesterases (PDEs) comprise a family of enzymes that modulate the immune response, inflammation, and memory, among many other functions. There are three types of PDEs: cAMP-specific, cGMP-specific, and dual-specific. Here we describe the mechanism of nucleotide selectivity on the basis of high-resolution co-crystal structures of the cAMP-specific PDE4B and PDE4D with AMP, the cGMP-specific PDE5A with GMP, and the apo-structure of the dual-specific PDE1B. These structures show that an invariant glutamine functions as the key specificity determinant by a "glutamine switch" mechanism for recognizing the purine moiety in cAMP or cGMP. The surrounding residues anchor the glutamine residue in different orientations for cAMP and for cGMP. The PDE1B structure shows that in dual-specific PDEs a key histidine residue may enable the invariant glutamine to toggle between cAMP and cGMP. The structural understanding of nucleotide binding enables the design of new PDE inhibitors that may treat diseases in which cyclic nucleotides play a critical role.

PubMed: 15260978
DOI: 10.1016/j.molcel.2004.07.005

実験手法

X-RAY DIFFRACTION (1.3 Å)