[English] 日本語
Yorodumi
- PDB-7d9s: Structure of huamn soluble guanylate cyclase in the YC1 and NO-bo... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7d9s
TitleStructure of huamn soluble guanylate cyclase in the YC1 and NO-bound state
Components(Guanylate cyclase soluble subunit ...) x 2
KeywordsSIGNALING PROTEIN / soluble guanylate cyclase
Function / homology
Function and homology information


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
Haem NO binding associated domain superfamily / Haem NO binding associated / Heme NO binding associated / Heme NO-binding / H-NOX domain superfamily / Haem-NO-binding / Adenylyl cyclase class-4/guanylyl cyclase, conserved site / Guanylate cyclase signature. / NO signalling/Golgi transport ligand-binding domain superfamily / Adenylyl- / guanylyl cyclase, catalytic domain ...Haem NO binding associated domain superfamily / Haem NO binding associated / Heme NO binding associated / Heme NO-binding / H-NOX domain superfamily / Haem-NO-binding / Adenylyl cyclase class-4/guanylyl cyclase, conserved site / Guanylate cyclase signature. / NO signalling/Golgi transport ligand-binding domain superfamily / Adenylyl- / guanylyl cyclase, catalytic domain / Adenylyl cyclase class-3/4/guanylyl cyclase / Adenylate and Guanylate cyclase catalytic domain / Guanylate cyclase domain profile. / Nucleotide cyclase
Similarity search - Domain/homology
PHOSPHOMETHYLPHOSPHONIC ACID GUANYLATE ESTER / PROTOPORPHYRIN IX CONTAINING FE / Chem-YC1 / Guanylate cyclase soluble subunit alpha-1 / Guanylate cyclase soluble subunit beta-1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.9 Å
AuthorsChen, L. / Liu, R. / Kang, Y.
Funding support China, 4items
OrganizationGrant numberCountry
Ministry of Science and Technology (MoST, China)2016YFA0502004 China
National Natural Science Foundation of China (NSFC)31622021 China
National Natural Science Foundation of China (NSFC)31821091 China
National Natural Science Foundation of China (NSFC)31870833 China
CitationJournal: Nat Commun / Year: 2021
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
DepositionOct 14, 2020Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Aug 11, 2021Provider: repository / Type: Initial release
Revision 1.1Oct 13, 2021Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.identifier_ORCID / _citation_author.name
Revision 1.2May 29, 2024Group: Data collection / Refinement description / Category: chem_comp_atom / chem_comp_bond / refine / Item: _refine.ls_d_res_high / _refine.ls_d_res_low

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-30619
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Guanylate cyclase soluble subunit alpha-1
B: Guanylate cyclase soluble subunit beta-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)149,6567
Polymers148,1662
Non-polymers1,4915
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area14550 Å2
ΔGint-134 kcal/mol
Surface area46110 Å2

-
Components

-
Guanylate cyclase soluble subunit ... , 2 types, 2 molecules AB

#1: Protein Guanylate cyclase soluble subunit alpha-1 / GCS-alpha-1 / Guanylate cyclase soluble subunit alpha-3 / GCS-alpha-3 / Soluble guanylate cyclase ...GCS-alpha-1 / Guanylate cyclase soluble subunit alpha-3 / GCS-alpha-3 / Soluble guanylate cyclase large subunit


Mass: 77566.484 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: GenBank: AAH28384.1 / Source: (gene. exp.) Homo sapiens (human) / Gene: GUCY1A1, GUC1A3, GUCSA3, GUCY1A3 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q02108, guanylate cyclase
#2: Protein Guanylate cyclase soluble subunit beta-1 / GCS-beta-1 / Guanylate cyclase soluble subunit beta-3 / GCS-beta-3 / Soluble guanylate cyclase small subunit


Mass: 70599.320 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GUCY1B1, GUC1B3, GUCSB3, GUCY1B3 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q02153, guanylate cyclase

-
Non-polymers , 4 types, 5 molecules

#3: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Mg
#4: Chemical ChemComp-YC1 / [5-[1-(phenylmethyl)indazol-3-yl]furan-2-yl]methanol


Mass: 304.343 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C19H16N2O2 / Feature type: SUBJECT OF INVESTIGATION
#5: Chemical ChemComp-HEM / PROTOPORPHYRIN IX CONTAINING FE / HEME


Mass: 616.487 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C34H32FeN4O4
#6: Chemical ChemComp-G2P / PHOSPHOMETHYLPHOSPHONIC ACID GUANYLATE ESTER


Mass: 521.208 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C11H18N5O13P3 / Comment: GMP-CPP, energy-carrying molecule analogue*YM

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: human soluble guanylate cyclase / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT
Source (natural)