4Z07

Co-crystal structure of the tandem CNB (CNB-A/B) domains of human PKG I beta with cGMP

4Z07 の概要

• エントリーDOI: 10.2210/pdb4z07/pdb
• 分子名称: cGMP-dependent protein kinase 1, CYCLIC GUANOSINE MONOPHOSPHATE, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: cgmp-binding domains, cgmp mediated dimeric interface, allosteric regulatory domain, serine-threonine kinase, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 89930.95

構造登録者

Kim, J.J.,Reger, A.S.,Arold, S.T.,Kim, C. (登録日: 2015-03-25, 公開日: 2016-04-13, 最終更新日: 2023-09-27)

主引用文献

Kim, J.J.,Lorenz, R.,Arold, S.T.,Reger, A.S.,Sankaran, B.,Casteel, D.E.,Herberg, F.W.,Kim, C.
Crystal Structure of PKG I:cGMP Complex Reveals a cGMP-Mediated Dimeric Interface that Facilitates cGMP-Induced Activation.
Structure, 24:710-720, 2016

PubMed Abstract: Cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) is a key regulator of smooth muscle and vascular tone and represents an important drug target for treating hypertensive diseases and erectile dysfunction. Despite its importance, its activation mechanism is not fully understood. To understand the activation mechanism, we determined a 2.5 Å crystal structure of the PKG I regulatory (R) domain bound with cGMP, which represents the activated state. Although we used a monomeric domain for crystallization, the structure reveals that two R domains form a symmetric dimer where the cGMP bound at high-affinity pockets provide critical dimeric contacts. Small-angle X-ray scattering and mutagenesis support this dimer model, suggesting that the dimer interface modulates kinase activation. Finally, structural comparison with the homologous cyclic AMP-dependent protein kinase reveals that PKG is drastically different from protein kinase A in its active conformation, suggesting a novel activation mechanism for PKG.

PubMed: 27066748
DOI: 10.1016/j.str.2016.03.009

実験手法

X-RAY DIFFRACTION (2.5 Å)