7D9S

Structure of huamn soluble guanylate cyclase in the YC1 and NO-bound state

7D9S の概要

• エントリーDOI: 10.2210/pdb7d9s/pdb
• EMDBエントリー: 30619
• 分子名称: Guanylate cyclase soluble subunit alpha-1, Guanylate cyclase soluble subunit beta-1, MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: soluble guanylate cyclase, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 149656.45

構造登録者

Chen, L.,Liu, R.,Kang, Y. (登録日: 2020-10-14, 公開日: 2021-08-11, 最終更新日: 2024-05-29)

主引用文献

Liu, R.,Kang, Y.,Chen, L.
Activation mechanism of human soluble guanylate cyclase by stimulators and activators.
Nat Commun, 12:5492-5492, 2021

PubMed Abstract: Soluble guanylate cyclase (sGC) is the receptor for nitric oxide (NO) in human. It is an important validated drug target for cardiovascular diseases. sGC can be pharmacologically activated by stimulators and activators. However, the detailed structural mechanisms, through which sGC is recognized and positively modulated by these drugs at high spacial resolution, are poorly understood. Here, we present cryo-electron microscopy structures of human sGC in complex with NO and sGC stimulators, YC-1 and riociguat, and also in complex with the activator cinaciguat. These structures uncover the molecular details of how stimulators interact with residues from both β H-NOX and CC domains, to stabilize sGC in the extended active conformation. In contrast, cinaciguat occupies the haem pocket in the β H-NOX domain and sGC shows both inactive and active conformations. These structures suggest a converged mechanism of sGC activation by pharmacological compounds.

PubMed: 34535643
DOI: 10.1038/s41467-021-25617-0

実験手法

ELECTRON MICROSCOPY (3.9 Å)