[English] 日本語
Yorodumi
- PDB-9m4t: CryoEM structure of the alpha1AAR complex with silodosin -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9m4t
TitleCryoEM structure of the alpha1AAR complex with silodosin
ComponentsAlpha-1A adrenergic receptor
KeywordsMEMBRANE PROTEIN / GPCR / Alpha1AAR / Silodosin
Function / homology
Function and homology information


negative regulation of heart rate involved in baroreceptor response to increased systemic arterial blood pressure / alpha1-adrenergic receptor activity / norepinephrine-epinephrine vasoconstriction involved in regulation of systemic arterial blood pressure / positive regulation of heart rate by epinephrine-norepinephrine / positive regulation of the force of heart contraction by epinephrine-norepinephrine / pilomotor reflex / phospholipase C-activating adrenergic receptor signaling pathway / neuron-glial cell signaling / cell growth involved in cardiac muscle cell development / positive regulation of action potential ...negative regulation of heart rate involved in baroreceptor response to increased systemic arterial blood pressure / alpha1-adrenergic receptor activity / norepinephrine-epinephrine vasoconstriction involved in regulation of systemic arterial blood pressure / positive regulation of heart rate by epinephrine-norepinephrine / positive regulation of the force of heart contraction by epinephrine-norepinephrine / pilomotor reflex / phospholipase C-activating adrenergic receptor signaling pathway / neuron-glial cell signaling / cell growth involved in cardiac muscle cell development / positive regulation of action potential / positive regulation of smooth muscle contraction / adult heart development / Adrenoceptors / positive regulation of cardiac muscle hypertrophy / smooth muscle contraction / adenylate cyclase-activating adrenergic receptor signaling pathway / response to hormone / positive regulation of vasoconstriction / positive regulation of cardiac muscle contraction / negative regulation of autophagy / positive regulation of synaptic transmission, GABAergic / caveola / MAPK cascade / G alpha (12/13) signalling events / cell-cell signaling / positive regulation of cytosolic calcium ion concentration / phospholipase C-activating G protein-coupled receptor signaling pathway / nuclear membrane / G alpha (q) signalling events / positive regulation of ERK1 and ERK2 cascade / positive regulation of MAPK cascade / intracellular signal transduction / G protein-coupled receptor signaling pathway / protein heterodimerization activity / response to xenobiotic stimulus / negative regulation of cell population proliferation / intracellular membrane-bounded organelle / apoptotic process / signal transduction / nucleoplasm / nucleus / plasma membrane / cytosol / cytoplasm
Similarity search - Function
Alpha 1A adrenoceptor / Adrenoceptor family / Serpentine type 7TM GPCR chemoreceptor Srsx / G-protein coupled receptors family 1 signature. / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / 7 transmembrane receptor (rhodopsin family)
Similarity search - Domain/homology
: / Alpha-1A adrenergic receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.19 Å
AuthorsLiu, S.S. / Guo, Q. / Wang, D.D. / Tao, Y.Y. / Jiao, H.Z.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC) China
CitationJournal: J Biol Chem / Year: 2025
Title: Molecular mechanism of antagonists recognition and regulation of the α- adrenoceptor. (α-Adrenoceptor Antagonist Recognition).
Authors: Sisi Liu / Haizhan Jiao / Yuyong Tao / Dandan Wang / Qiong Guo /
Abstract: The α-adrenoceptor (αAR) is a critically important class of G protein-coupled receptors (GPCRs), comprising three subtypes: αAR, αAR, and αAR. Currently, drugs targeting αAR have been used in ...The α-adrenoceptor (αAR) is a critically important class of G protein-coupled receptors (GPCRs), comprising three subtypes: αAR, αAR, and αAR. Currently, drugs targeting αAR have been used in the treatment of various diseases. Notably, antagonists of αAR play a pivotal role in the management of benign prostatic hyperplasia (BPH). In recent years, researchers have developed selective antagonists for the αAR subtype that have a minimal impact on blood pressure for the treatment of BPH. However, these agents still exhibit certain side effects, necessitating the continuous development of new medications to mitigate adverse reactions while achieving more precise regulation. We report the cryo-EM structures of the αAR selective antagonist doxazosin and the αAR subtype selective antagonist silodosin in complex with αAR, demonstrating that M292 and V185 are key residues that confer subtype selectivity to silodosin. Additionally, modifications to αAR enhanced silodosin's inhibitory efficacy against αAR. These findings deepen our understanding of the recognition patterns of αAR antagonists, revealing the molecular principles underlying the selective binding of silodosin to αAR and promoting further research and development of subtype selective drugs targeting αAR.
History
DepositionMar 4, 2025Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Jul 2, 2025Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Alpha-1A adrenergic receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,2882
Polymers35,7931
Non-polymers4961
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

#1: Protein Alpha-1A adrenergic receptor / Alpha-1A adrenoreceptor / Alpha-1A adrenoceptor / Alpha-1C adrenergic receptor / Alpha-adrenergic receptor 1c


Mass: 35792.500 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ADRA1A, ADRA1C / Production host: Homo sapiens (human) / References: UniProt: P35348
#2: Chemical ChemComp-A1EMV / Silodosin


Mass: 495.534 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C25H32F3N3O4
Has ligand of interestN
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: CryoEM structure of the the alpha1AAR complex with silodosin
Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT
Molecular weightExperimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.4
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2300 nm / Nominal defocus min: 1700 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

-
Processing

CTF correctionType: NONE
3D reconstructionResolution: 3.19 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 3759439 / Symmetry type: POINT

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more