[English] 日本語
Yorodumi
- EMDB-64368: Cryo-EM structure of human OAT1 in complex with olmesartan and br... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-64368
TitleCryo-EM structure of human OAT1 in complex with olmesartan and bromide ion.
Map dataCryo-EM map of human OAT1-olmesartan-bromide complex.
Sample
  • Complex: Human OAT1 in complex with olmesartan and bromide
    • Protein or peptide: Solute carrier family 22 member 6
  • Ligand: BROMIDE ION
  • Ligand: Olmesartan
Keywordsdrug-drug interaction / transporter / substrate / organic anion. / MEMBRANE PROTEIN
Function / homology
Function and homology information


renal tubular secretion / alpha-ketoglutarate transport / alpha-ketoglutarate transmembrane transporter activity / Organic anion transport by SLC22 transporters / sodium-independent organic anion transport / : / metanephric proximal tubule development / prostaglandin transport / prostaglandin transmembrane transporter activity / organic anion transport ...renal tubular secretion / alpha-ketoglutarate transport / alpha-ketoglutarate transmembrane transporter activity / Organic anion transport by SLC22 transporters / sodium-independent organic anion transport / : / metanephric proximal tubule development / prostaglandin transport / prostaglandin transmembrane transporter activity / organic anion transport / solute:inorganic anion antiporter activity / : / monoatomic anion transport / chloride ion binding / antiporter activity / transmembrane transporter activity / xenobiotic transmembrane transporter activity / basal plasma membrane / caveola / basolateral plasma membrane / protein-containing complex / extracellular exosome / identical protein binding / plasma membrane
Similarity search - Function
Organic cation transport protein/SVOP / Major facilitator, sugar transporter-like / Sugar (and other) transporter / Major facilitator superfamily domain / Major facilitator superfamily (MFS) profile. / MFS transporter superfamily
Similarity search - Domain/homology
Solute carrier family 22 member 6
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.45 Å
AuthorsJeon HM / Eun J / Kim KH / Kim Y
Funding support Korea, Republic Of, 1 items
OrganizationGrant numberCountry
National Research Foundation (NRF, Korea)NRF-2022R1A5A10313611 Korea, Republic Of
CitationJournal: Structure / Year: 2025
Title: Cryo-EM structures of human OAT1 reveal drug binding and inhibition mechanisms.
Authors: Hyung-Min Jeon / Jisung Eun / Kelly H Kim / Youngjin Kim /
Abstract: The organic anion transporter 1 (OAT1) plays a key role in excreting waste from organic drug metabolism and contributes significantly to drug-drug interactions and drug disposition. However, the ...The organic anion transporter 1 (OAT1) plays a key role in excreting waste from organic drug metabolism and contributes significantly to drug-drug interactions and drug disposition. However, the structural basis of specific substrate and inhibitor transport by human OAT1 (hOAT1) has remained elusive. We determined four cryogenic electron microscopy (cryo-EM) structures of hOAT1 in its inward-facing conformation: the apo form, the substrate (olmesartan)-bound form with different anions, and the inhibitor (probenecid)-bound form. Structural and functional analyses revealed that Ser203 has an auxiliary role in chloride coordination, and it is a critical residue modulating olmesartan transport via chloride ion interactions. Structural comparisons indicate that inhibitors not only compete with substrates, but also obstruct substrate exit and entry from the cytoplasmic side, thereby increasing inhibitor retention. The findings can support drug development by providing insights into substrate recognition and the mechanism by which inhibitors arrest the OAT1 transport cycle.
History
DepositionApr 24, 2025-
Header (metadata) releaseNov 5, 2025-
Map releaseNov 5, 2025-
UpdateNov 5, 2025-
Current statusNov 5, 2025Processing site: PDBj / Status: Released

-
Structure visualization

Supplemental images

emd_64368.png

Downloads & links

-
Map

FileDownload / File: emd_64368.map.gz / Format: CCP4 / Size: 83.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationCryo-EM map of human OAT1-olmesartan-bromide complex.
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.82 Å/pix.
x 280 pix.
= 230.944 Å		0.82 Å/pix.
x 280 pix.
= 230.944 Å		0.82 Å/pix.
x 280 pix.
= 230.944 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.8248 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.15
Minimum - Maximum-0.9568511 - 1.4021755
Average (Standard dev.)0.00039303894 (±0.025652524)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions280280280
Spacing280280280
CellA=B=C: 230.944 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Mask #1

Fileemd_64368_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: Cryo-EM half map of human OAT1-olmesartan-bromide complex.

Fileemd_64368_half_map_1.map
AnnotationCryo-EM half map of human OAT1-olmesartan-bromide complex.
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: Cryo-EM half map of human OAT1-olmesartan-bromide complex.

Fileemd_64368_half_map_2.map
AnnotationCryo-EM half map of human OAT1-olmesartan-bromide complex.
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Human OAT1 in complex with olmesartan and bromide

EntireName: Human OAT1 in complex with olmesartan and bromide
Components
  • Complex: Human OAT1 in complex with olmesartan and bromide
    • Protein or peptide: Solute carrier family 22 member 6
  • Ligand: BROMIDE ION
  • Ligand: Olmesartan

-
Supramolecule #1: Human OAT1 in complex with olmesartan and bromide

SupramoleculeName: Human OAT1 in complex with olmesartan and bromide / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Details: human OAT1 in complex with olmesartan and, adopting inward facing conformation and embedded in LMNG/CHS micelle
Source (natural)Organism: Homo sapiens (human) / Organ: kidney / Location in cell: Plasma membrane
Molecular weightTheoretical: 62 KDa

-
Macromolecule #1: Solute carrier family 22 member 6

MacromoleculeName: Solute carrier family 22 member 6 / type: protein_or_peptide / ID: 1
Details: human OAT1 in complex with olmesartan and bromide ion, adopting inward facing conformation and embedded in LMNG/CHS micelle
Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human) / Organ: Kidney / Cell: Epithelial
Molecular weightTheoretical: 61.869027 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MAFNDLLQQV GGVGRFQQIQ VTLVVLPLLL MASHNTLQNF TAAIPTHHCR PPADANLSKN GGLEVWLPRD RQGQPESCLR FTSPQWGLP FLNGTEANGT GATEPCTDGW IYDNSTFPST IVTEWDLVCS HRALRQLAQS LYMVGVLLGA MVFGYLADRL G RRKVLILN ...String:
MAFNDLLQQV GGVGRFQQIQ VTLVVLPLLL MASHNTLQNF TAAIPTHHCR PPADANLSKN GGLEVWLPRD RQGQPESCLR FTSPQWGLP FLNGTEANGT GATEPCTDGW IYDNSTFPST IVTEWDLVCS HRALRQLAQS LYMVGVLLGA MVFGYLADRL G RRKVLILN YLQTAVSGTC AAFAPNFPIY CAFRLLSGMA LAGISLNCMT LNVEWMPIHT RACVGTLIGY VYSLGQFLLA GV AYAVPHW RHLQLLVSAP FFAFFIYSWF FIESARWHSS SGRLDLTLRA LQRVARINGK REEGAKLSME VLRASLQKEL TMG KGQASA MELLRCPTLR HLFLCLSMLW FATSFAYYGL VMDLQGFGVS IYLIQVIFGA VDLPAKLVGF LVINSLGRRP AQMA ALLLA GICILLNGVI PQDQSIVRTS LAVLGKGCLA ASFNCIFLYT GELYPTMIRQ TGMGMGSTMA RVGSIVSPLV SMTAE LYPS MPLFIYGAVP VAASAVTVLL PETLGQPLPD TVQDLESRWA PTQKEAGIYP RKGKQTRQQQ EHQKYMVPLQ ASAQEK NGL

UniProtKB: Solute carrier family 22 member 6

-
Macromolecule #2: BROMIDE ION

MacromoleculeName: BROMIDE ION / type: ligand / ID: 2 / Number of copies: 1 / Formula: BR
Molecular weightTheoretical: 79.904 Da
Chemical component information

ChemComp-BR:
BROMIDE ION

-
Macromolecule #3: Olmesartan

MacromoleculeName: Olmesartan / type: ligand / ID: 3 / Number of copies: 1 / Formula: OLM
Molecular weightTheoretical: 446.502 Da
Chemical component information

ChemComp-OLM:
Olmesartan

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration18 mg/mL
BufferpH: 7.5
Component:
ConcentrationFormulaName
150.0 mMNaBrsodium bromide
20.0 mMC8H18N2O4SHEPES
20.0 mMKNaC4H4O6sodium potassium tartrate

Details: 20 mM HEPES, 150 mM NaCl, 20 mM Na/K-tartrate, 0.0015% LMNG, 0.00015% CHS
GridModel: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 60 sec. / Pretreatment - Pressure: 0.025 kPa
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 283 K / Instrument: FEI VITROBOT MARK IV
DetailsThis sample is a complex formed by composition of human OAT1, Fab targeting C-terminus of human OAT1, and the substrate olmesartan, purified in bromide buffer.

-
Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Digitization - Dimensions - Width: 5760 pixel / Digitization - Dimensions - Height: 4092 pixel / Number grids imaged: 3 / Number real images: 32271 / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 105000
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

Particle selectionNumber selected: 10849658
CTF correctionSoftware - Name: cryoSPARC (ver. 4.4.1) / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionNumber classes used: 1 / Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.45 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 4.4.1) / Number images used: 118678
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 4.4.1)
Final angle assignmentType: NOT APPLICABLE
Final 3D classificationNumber classes: 3 / Avg.num./class: 58934 / Software - Name: RELION (ver. 5.0)
FSC plot (resolution estimation)

-
Atomic model buiding 1

Initial modelPDB ID:

9klz


Chain - Chain ID: A / Chain - Source name: PDB / Chain - Initial model type: experimental model
RefinementProtocol: RIGID BODY FIT
Output model

PDB-9unx:
Cryo-EM structure of human OAT1 in complex with olmesartan and bromide ion.

+
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