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- EMDB-14725: Structure of human OCT3 in complex with inhibitor Corticosterone -
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Open data
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Basic information
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Title | Structure of human OCT3 in complex with inhibitor Corticosterone | |||||||||
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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 | single particle reconstruction / cryo EM / Resolution: 3.67 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. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 9.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 16 KB 16 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 12.5 KB | Display | ![]() |
Images | ![]() | 72.5 KB | ||
Others | ![]() ![]() | 152.3 MB 152.3 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 444.1 KB | Display | ![]() |
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Full document | ![]() | 443.6 KB | Display | |
Data in XML | ![]() | 19.6 KB | Display | |
Data in CIF | ![]() | 25.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7zh6MC ![]() 7zh0C ![]() 7zhaC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 0.66 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: half1
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Annotation | half1 | ||||||||||||
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Density Histograms |
-Half map: half2
File | emd_14725_half_map_2.map | ||||||||||||
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Annotation | half2 | ||||||||||||
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Density Histograms |
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Sample components
-Entire : human OCT3 in complex with inhibitor Corticosterone
Entire | Name: human OCT3 in complex with inhibitor Corticosterone |
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Components |
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-Supramolecule #1: human OCT3 in complex with inhibitor Corticosterone
Supramolecule | Name: human OCT3 in complex with inhibitor Corticosterone / type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Solute carrier family 22 member 3
Macromolecule | Name: Solute carrier family 22 member 3 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 61.332836 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MPSFDEALQR VGEFGRFQRR VFLLLCLTGV TFAFLFVGVV FLGTQPDHYW CRGPSAAALA ERCGWSPEEE WNRTAPASRG PEPPERRGR CQRYLLEAAN DSASATSALS CADPLAAFPN RSAPLVPCRG GWRYAQAHST IVSEFDLVCV NAWMLDLTQA I LNLGFLTG ...String: MPSFDEALQR VGEFGRFQRR VFLLLCLTGV TFAFLFVGVV FLGTQPDHYW CRGPSAAALA ERCGWSPEEE WNRTAPASRG PEPPERRGR CQRYLLEAAN DSASATSALS CADPLAAFPN RSAPLVPCRG GWRYAQAHST IVSEFDLVCV NAWMLDLTQA I LNLGFLTG AFTLGYAADR YGRIVIYLLS CLGVGVTGVV VAFAPNFPVF VIFRFLQGVF GKGTWMTCYV IVTEIVGSKQ RR IVGIVIQ MFFTLGIIIL PGIAYFIPNW QGIQLAITLP SFLFLLYYWV VPESPRWLIT RKKGDKALQI LRRIAKCNGK YLS SNYSEI TVTDEEVSNP SFLDLVRTPQ MRKCTLILMF AWFTSAVVYQ GLVMRLGIIG GNLYIDFFIS GVVELPGALL ILLT IERLG RRLPFAASNI VAGVACLVTA FLPEGIAWLR TTVATLGRLG ITMAFEIVYL VNSELYPTTL RNFGVSLCSG LCDFG GIIA PFLLFRLAAV WLELPLIIFG ILASICGGLV MLLPETKGIA LPETVDDVEK LGSPHSCKCG RNKKTPVSRS HL |
-Macromolecule #2: CORTICOSTERONE
Macromolecule | Name: CORTICOSTERONE / type: ligand / ID: 2 / Number of copies: 1 / Formula: C0R |
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Molecular weight | Theoretical: 346.461 Da |
Chemical component information | ![]() ChemComp-C0R: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | #0 - Image recording ID: 1 / #0 - Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / #0 - Average electron dose: 49.0 e/Å2 / #0 - Details: Dataset 1 / #1 - Image recording ID: 2 / #1 - Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / #1 - Average electron dose: 51.0 e/Å2 / #1 - Details: Dataset 2 / #2 - Image recording ID: 3 / #2 - Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / #2 - Average electron dose: 61.0 e/Å2 / #2 - Details: Dataset 3 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.0 µm / Nominal defocus min: 0.5 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |