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- PDB-7d9s: Structure of huamn soluble guanylate cyclase in the YC1 and NO-bo... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7d9s | |||||||||||||||
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Title | Structure of huamn soluble guanylate cyclase in the YC1 and NO-bound state | |||||||||||||||
![]() | (Guanylate cyclase soluble subunit ...) x 2 | |||||||||||||||
![]() | SIGNALING PROTEIN / soluble guanylate cyclase | |||||||||||||||
Function / homology | ![]() retrograde trans-synaptic signaling by nitric oxide, modulating synaptic transmission / cytidylate cyclase activity / trans-synaptic signaling by nitric oxide, modulating synaptic transmission / guanylate cyclase / guanylate cyclase complex, soluble / cGMP biosynthetic process / guanylate cyclase activity / presynaptic active zone cytoplasmic component / response to oxygen levels / Nitric oxide stimulates guanylate cyclase ...retrograde trans-synaptic signaling by nitric oxide, modulating synaptic transmission / cytidylate cyclase activity / trans-synaptic signaling by nitric oxide, modulating synaptic transmission / guanylate cyclase / guanylate cyclase complex, soluble / cGMP biosynthetic process / guanylate cyclase activity / presynaptic active zone cytoplasmic component / response to oxygen levels / Nitric oxide stimulates guanylate cyclase / relaxation of vascular associated smooth muscle / adenylate cyclase activity / blood circulation / positive regulation of nitric oxide mediated signal transduction / cGMP-mediated signaling / Smooth Muscle Contraction / cellular response to nitric oxide / GABA-ergic synapse / nitric oxide mediated signal transduction / nitric oxide-cGMP-mediated signaling / Hsp90 protein binding / regulation of blood pressure / signaling receptor activity / glutamatergic synapse / heme binding / protein-containing complex binding / GTP binding / metal ion binding / cytosol Similarity search - Function | |||||||||||||||
Biological species | ![]() | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.9 Å | |||||||||||||||
![]() | Chen, L. / Liu, R. / Kang, Y. | |||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Activation mechanism of human soluble guanylate cyclase by stimulators and activators. Authors: Rui Liu / Yunlu Kang / Lei Chen / ![]() 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 ...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. | |||||||||||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 203.6 KB | Display | ![]() |
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PDB format | ![]() | 152.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 949.3 KB | Display | ![]() |
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Full document | ![]() | 966.1 KB | Display | |
Data in XML | ![]() | 34.5 KB | Display | |
Data in CIF | ![]() | 52 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 30619MC ![]() 7d9rC ![]() 7d9tC ![]() 7d9uC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Guanylate cyclase soluble subunit ... , 2 types, 2 molecules AB
#1: Protein | Mass: 77566.484 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: GenBank: AAH28384.1 / Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Protein | Mass: 70599.320 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Non-polymers , 4 types, 5 molecules ![](data/chem/img/MG.gif)
![](data/chem/img/YC1.gif)
![](data/chem/img/HEM.gif)
![](data/chem/img/G2P.gif)
![](data/chem/img/YC1.gif)
![](data/chem/img/HEM.gif)
![](data/chem/img/G2P.gif)
#3: Chemical | #4: Chemical | ChemComp-YC1 / [ | #5: Chemical | ChemComp-HEM / | #6: Chemical | ChemComp-G2P / | |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: human soluble guanylate cyclase / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K2 QUANTUM (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.15.2_3472: / Classification: refinement | ||||||||||||||||||||||||
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EM software | Name: RELION / Version: 3 / Category: 3D reconstruction | ||||||||||||||||||||||||
CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 321343 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Resolution: 3.9→3.9 Å / SU ML: 1.16 / σ(F): 0.19 / Phase error: 50.3 / Stereochemistry target values: MLHL /
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||
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