scholarly journals Interfacial Residues Promote an Optimal Alignment of the Catalytic Center in Human Soluble Guanylate Cyclase: Heterodimerization Is Required but Not Sufficient for Activity

Biochemistry ◽  
2014 ◽  
Vol 53 (13) ◽  
pp. 2153-2165 ◽  
Author(s):  
Franziska Seeger ◽  
Royston Quintyn ◽  
Akiko Tanimoto ◽  
Gareth J. Williams ◽  
John A. Tainer ◽  
...  
Keyword(s):  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Optimal Alignment ◽  
Catalytic Center ◽  
Human Soluble Guanylate Cyclase

Interfacial residues promote an optimal alignment of the catalytic center in soluble guanylate cyclase

Nitric Oxide ◽  
2014 ◽  
Vol 42 ◽  
pp. 112
Author(s):  
Elsa Garcin ◽  
Franziska Seeger ◽  
Royston Quintyn ◽  
Akiko Tanimoto ◽  
Gareth Williams ◽  
...  
Keyword(s):  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Optimal Alignment ◽  
Catalytic Center

Interfacial residues promote an optimal alignment of the catalytic center in soluble guanylate cyclase

Nitric Oxide ◽  
2014 ◽  
Vol 42 ◽  
pp. 152-153
Author(s):  
Elsa Garcin ◽  
Franziska Seeger ◽  
Royston Quintyn ◽  
Akiko Tanimoto ◽  
Gareth Williams ◽  
...  
Keyword(s):  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Optimal Alignment ◽  
Catalytic Center

scholarly journals Probing the Structural Dynamics of the Catalytic Domain of Human Soluble Guanylate Cyclase

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Rana Rehan Khalid ◽  
Arooma Maryam ◽  
Osman Ugur Sezerman ◽  
Efstratios Mylonas ◽  
Abdul Rauf Siddiqi ◽  
...  
Keyword(s):  
Structural Dynamics ◽  
Guanylate Cyclase ◽  
Catalytic Domain ◽  
Soluble Guanylate Cyclase ◽  
Human Soluble Guanylate Cyclase

scholarly journals Structural insights into the mechanism of human soluble guanylate cyclase

Nature ◽  
2019 ◽  
Vol 574 (7777) ◽  
pp. 206-210 ◽  
Author(s):  
Yunlu Kang ◽  
Rui Liu ◽  
Jing-Xiang Wu ◽  
Lei Chen
Keyword(s):  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Human Soluble Guanylate Cyclase ◽  
Structural Insights

scholarly journals Activation mechanism of human soluble guanylate cyclase by stimulators and activators

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Rui Liu ◽  
Yunlu Kang ◽  
Lei Chen
Keyword(s):  
Electron Microscopy ◽  
Guanylate Cyclase ◽  
Drug Target ◽  
Soluble Guanylate Cyclase ◽  
Activation Mechanism ◽  
Active Conformation ◽  
Cryo Electron Microscopy ◽  
Human Soluble Guanylate Cyclase ◽  
Structural Mechanisms ◽  
Sgc Stimulators

AbstractSoluble 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.

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