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Open data
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Basic information
Entry | Database: PDB / ID: 7zha | ||||||
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Title | Structure of human OCT3 in complex with inhibitor decynium-22 | ||||||
![]() | Solute carrier family 22 member 3 | ||||||
![]() | MEMBRANE PROTEIN / Organic cation transporter / major-facilitator superfamily / SLC22 family / Corticosterone sensitive protein / membrane transport / decynium-22 | ||||||
Function / homology | ![]() 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 | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.55 Å | ||||||
![]() | Khanppnavar, B. / Korkhov, V. | ||||||
Funding support | ![]()
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![]() | ![]() 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. | ||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 92.8 KB | Display | ![]() |
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PDB format | ![]() | 71.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1022.6 KB | Display | ![]() |
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Full document | ![]() | 1 MB | Display | |
Data in XML | ![]() | 34.8 KB | Display | |
Data in CIF | ![]() | 49.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 14728MC ![]() 7zh0C ![]() 7zh6C M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 61332.836 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#2: Chemical | ChemComp-JDW / |
Has ligand of interest | Y |
-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 OCT3 reconstituted in lipid nanodisc and in complex with inhibitor decynium-22 Type: COMPLEX / Entity ID: #1 / Source: NATURAL |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 8 |
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 / Nominal defocus max: 3000 nm / Nominal defocus min: 500 nm | |||||||||||||||
Image recording |
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Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.55 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 130654 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | B value: 100 / Protocol: AB INITIO MODEL / Space: REAL | ||||||||||||||||||||||||
Refine LS restraints |
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