[English] 日本語
Yorodumi
- PDB-7zh0: Structure of human OCT3 in lipid nanodisc -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7zh0
TitleStructure of human OCT3 in lipid nanodisc
ComponentsSolute carrier family 22 member 3
KeywordsMEMBRANE PROTEIN / Organic cation transporter / major-facilitator superfamily / SLC22 family / Corticosterone sensitive protein / membrane transport
Function / homology
Function and homology information


histamine transport / epinephrine uptake / histamine metabolic process / monocarboxylic acid transport / serotonin transport / spermidine transmembrane transporter activity / quaternary ammonium group transmembrane transporter activity / quaternary ammonium group transport / epinephrine transport / purine-containing compound transmembrane transport ...histamine transport / epinephrine uptake / histamine metabolic process / monocarboxylic acid transport / serotonin transport / spermidine transmembrane transporter activity / quaternary ammonium group transmembrane transporter activity / quaternary ammonium group transport / epinephrine transport / purine-containing compound transmembrane transport / spermidine transport / organic cation transport / Organic cation transport / organic cation transmembrane transporter activity / histamine uptake / dopamine uptake / regulation of appetite / norepinephrine uptake / norepinephrine transport / toxin transmembrane transporter activity / Abacavir transmembrane transport / neurotransmitter transmembrane transporter activity / serotonin uptake / organic anion transport / dopamine transport / monoamine transmembrane transporter activity / monoamine transport / organic anion transmembrane transporter activity / xenobiotic transport / nuclear outer membrane / neurotransmitter transport / cellular detoxification / transport across blood-brain barrier / endomembrane system / monoatomic ion transport / mitochondrial membrane / presynapse / basolateral plasma membrane / apical plasma membrane / neuronal cell body / membrane / plasma membrane
Similarity search - Function
Organic cation transport protein/SVOP / Sugar transport proteins signature 1. / Sugar transporter, conserved site / Major facilitator superfamily / Major Facilitator Superfamily / Major facilitator superfamily domain / Major facilitator superfamily (MFS) profile. / MFS transporter superfamily
Similarity search - Domain/homology
Solute carrier family 22 member 3
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å
AuthorsKhanppnavar, B. / Korkhov, V. / Qi, C.
Funding support Switzerland, 1items
OrganizationGrant numberCountry
Swiss National Science Foundation198545 Switzerland
CitationJournal: Nat Commun / Year: 2022
Title: Structural basis of organic cation transporter-3 inhibition.
Authors: Basavraj Khanppnavar / Julian Maier / Freja Herborg / Ralph Gradisch / Erika Lazzarin / Dino Luethi / Jae-Won Yang / Chao Qi / Marion Holy / Kathrin Jäntsch / Oliver Kudlacek / Klaus ...Authors: Basavraj Khanppnavar / Julian Maier / Freja Herborg / Ralph Gradisch / Erika Lazzarin / Dino Luethi / Jae-Won Yang / Chao Qi / Marion Holy / Kathrin Jäntsch / Oliver Kudlacek / Klaus Schicker / Thomas Werge / Ulrik Gether / Thomas Stockner / Volodymyr M Korkhov / Harald H Sitte /
Abstract: Organic cation transporters (OCTs) facilitate the translocation of catecholamines, drugs and xenobiotics across the plasma membrane in various tissues throughout the human body. OCT3 plays a key role ...Organic cation transporters (OCTs) facilitate the translocation of catecholamines, drugs and xenobiotics across the plasma membrane in various tissues throughout the human body. OCT3 plays a key role in low-affinity, high-capacity uptake of monoamines in most tissues including heart, brain and liver. Its deregulation plays a role in diseases. Despite its importance, the structural basis of OCT3 function and its inhibition has remained enigmatic. Here we describe the cryo-EM structure of human OCT3 at 3.2 Å resolution. Structures of OCT3 bound to two inhibitors, corticosterone and decynium-22, define the ligand binding pocket and reveal common features of major facilitator transporter inhibitors. In addition, we relate the functional characteristics of an extensive collection of previously uncharacterized human genetic variants to structural features, thereby providing a basis for understanding the impact of OCT3 polymorphisms.
History
DepositionApr 5, 2022Deposition site: PDBE / Processing site: PDBE
Revision 1.0Nov 9, 2022Provider: repository / Type: Initial release
Revision 1.1Dec 7, 2022Group: Database references / Category: citation / Item: _citation.title
Revision 1.2Apr 19, 2023Group: 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

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Solute carrier family 22 member 3


Theoretical massNumber of molelcules
Total (without water)61,3331
Polymers61,3331
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area0 Å2
ΔGint0 kcal/mol
Surface area22850 Å2
MethodPISA

-
Components

#1: Protein Solute carrier family 22 member 3 / Extraneuronal monoamine transporter / EMT / Organic cation transporter 3


Mass: 61332.836 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SLC22A3, EMTH, OCT3 / Production host: Homo sapiens (human) / References: UniProt: O75751

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: human OCT3 in lipid nanodisc / Type: CELL / Entity ID: all / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 8
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: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 3000 nm / Nominal defocus min: 500 nm
Image recording
IDImaging-IDElectron dose (e/Å2)Film or detector modelDetails
1148GATAN K3 BIOQUANTUM (6k x 4k)Data set 1, 2 and 3
2149GATAN K3 BIOQUANTUM (6k x 4k)Data set 4

-
Processing

SoftwareName: PHENIX / Version: 1.19.2_4158: / Classification: refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 238702 / Symmetry type: POINT
Atomic model buildingB value: 80 / Protocol: AB INITIO MODEL / Space: REAL
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0043973
ELECTRON MICROSCOPYf_angle_d0.6465408
ELECTRON MICROSCOPYf_dihedral_angle_d4.516537
ELECTRON MICROSCOPYf_chiral_restr0.042630
ELECTRON MICROSCOPYf_plane_restr0.005671

+
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://pdbjlvh1.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