[English] 日本語
Yorodumi
- EMDB-46006: Outward-facing cyclosporine A-bound OATP1B1 with sybody 5 (Sb5) -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-46006
TitleOutward-facing cyclosporine A-bound OATP1B1 with sybody 5 (Sb5)
Map data
Sample
  • Complex: Outward-facing cyclosporine A-bound OATP1B1 with sybody 5
    • Protein or peptide: Solute carrier organic anion transporter family member 1B1
    • Protein or peptide: Sybody 5
  • Protein or peptide: Cyclosporin A
Keywordssolute carrier / sybody / membrane protein / drug-drug interactions / TRANSPORT PROTEIN
Function / homology
Function and homology information


Defective SLCO1B1 causes hyperbilirubinemia, Rotor type (HBLRR) / Organic anion transport by SLCO transporters / sodium-independent organic anion transport / : / thyroid hormone transmembrane transporter activity / prostaglandin transmembrane transporter activity / heme catabolic process / Atorvastatin ADME / organic anion transport / : ...Defective SLCO1B1 causes hyperbilirubinemia, Rotor type (HBLRR) / Organic anion transport by SLCO transporters / sodium-independent organic anion transport / : / thyroid hormone transmembrane transporter activity / prostaglandin transmembrane transporter activity / heme catabolic process / Atorvastatin ADME / organic anion transport / : / bile acid transmembrane transporter activity / Heme degradation / bile acid and bile salt transport / Recycling of bile acids and salts / monoatomic ion transport / xenobiotic metabolic process / basal plasma membrane / basolateral plasma membrane / membrane / plasma membrane
Similarity search - Function
Organic anion transporter polypeptide / Organic Anion Transporter Polypeptide (OATP) family / Kazal-type serine protease inhibitor domain / Kazal domain superfamily / Kazal domain / Kazal domain profile. / Major facilitator superfamily domain / Major facilitator superfamily (MFS) profile. / MFS transporter superfamily
Similarity search - Domain/homology
Solute carrier organic anion transporter family member 1B1
Similarity search - Component
Biological speciesHomo sapiens (human) / synthetic construct (others)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.41 Å
AuthorsSung MW / Lees JA / Han S
Funding support United States, 1 items
OrganizationGrant numberCountry
Other private United States
CitationJournal: J Biol Chem / Year: 2025
Title: Cyclosporine A sterically inhibits statin transport by solute carrier OATP1B1.
Authors: Min Woo Sung / Kuan Hu / Lea M Hurlimann / Joshua A Lees / Kimberly F Fennell / Mark A West / Chester Costales / Amilcar David Rodrigues / Iwan Zimmermann / Roger J P Dawson / Shenping Liu / Seungil Han /
Abstract: Members of the Organic Anion Transporter Polypeptides (OATP) are integral membrane proteins responsible for facilitating the transport of organic anions across the cell membrane. OATP1B1 (SLCO1B1), ...Members of the Organic Anion Transporter Polypeptides (OATP) are integral membrane proteins responsible for facilitating the transport of organic anions across the cell membrane. OATP1B1 (SLCO1B1), the prototypic OATP family member, is the most abundant uptake transporter in the liver and a key mediator of the hepatic uptake and clearance of numerous endogenous and xenobiotic compounds. It serves as a locus of important drug-drug interactions, such as those between statins and cyclosporine A, and carries the potential to enable liver-targeting therapeutics. In this study, we report cryo-EM structures of OATP1B1 and its complexes with one of its statin substrates, atorvastatin, and an inhibitor, cyclosporine A. This structural analysis has yielded insights into the mechanisms underlying the OATP1B1-mediated transport of statins and the inhibitory effect of cyclosporine A. These findings contribute to a better understanding of the molecular processes involved in drug transport and offer potential avenues for the development of targeted medications for liver-related conditions.
History
DepositionAug 1, 2024-
Header (metadata) releaseApr 16, 2025-
Map releaseApr 16, 2025-
UpdateMay 21, 2025-
Current statusMay 21, 2025Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_46006.png

Downloads & links

-
Map

FileDownload / File: emd_46006.map.gz / Format: CCP4 / Size: 52.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.1 Å/pix.
x 240 pix.
= 263.76 Å		1.1 Å/pix.
x 240 pix.
= 263.76 Å		1.1 Å/pix.
x 240 pix.
= 263.76 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.099 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.2
Minimum - Maximum-0.8286686 - 1.5281332
Average (Standard dev.)0.00024304156 (±0.024402058)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions240240240
Spacing240240240
CellA=B=C: 263.76 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #2

Fileemd_46006_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_46006_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Outward-facing cyclosporine A-bound OATP1B1 with sybody 5

EntireName: Outward-facing cyclosporine A-bound OATP1B1 with sybody 5
Components
  • Complex: Outward-facing cyclosporine A-bound OATP1B1 with sybody 5
    • Protein or peptide: Solute carrier organic anion transporter family member 1B1
    • Protein or peptide: Sybody 5
  • Protein or peptide: Cyclosporin A

-
Supramolecule #1: Outward-facing cyclosporine A-bound OATP1B1 with sybody 5

SupramoleculeName: Outward-facing cyclosporine A-bound OATP1B1 with sybody 5
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Solute carrier organic anion transporter family member 1B1

MacromoleculeName: Solute carrier organic anion transporter family member 1B1
type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 79.880977 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MHHHHHHHHH HDYKDDDDKE NLYFQGMDQN QHLNKTAEAQ PSENKKTRYC NGLKMFLAAL SLSFIAKTLG AIIMKSSIIH IERRFEISS SLVGFIDGSF EIGNLLVIVF VSYFGSKLHR PKLIGIGCFI MGIGGVLTAL PHFFMGYYRY SKETNINSSE N STSTLSTC ...String:
MHHHHHHHHH HDYKDDDDKE NLYFQGMDQN QHLNKTAEAQ PSENKKTRYC NGLKMFLAAL SLSFIAKTLG AIIMKSSIIH IERRFEISS SLVGFIDGSF EIGNLLVIVF VSYFGSKLHR PKLIGIGCFI MGIGGVLTAL PHFFMGYYRY SKETNINSSE N STSTLSTC LINQILSLNR ASPEIVGKGC LKESGSYMWI YVFMGNMLRG IGETPIVPLG LSYIDDFAKE GHSSLYLGIL NA IAMIGPI IGFTLGSLFS KMYVDIGYVD LSTIRITPTD SRWVGAWWLN FLVSGLFSII SSIPFFFLPQ TPNKPQKERK ASL SLHVLE TNDEKDQTAN LTNQGKNITK NVTGFFQSFK SILTNPLYVM FVLLTLLQVS SYIGAFTYVF KYVEQQYGQP SSKA NILLG VITIPIFASG MFLGGYIIKK FKLNTVGIAK FSCFTAVMSL SFYLLYFFIL CENKSVAGLT MTYDGNNPVT SHRDV PLSY CNSDCNCDES QWEPVCGNNG ITYISPCLAG CKSSSGNKKP IVFYNCSCLE VTGLQNRNYS AHLGECPRDD ACTRKF YFF VAIQVLNLFF SALGGTSHVM LIVKIVQPEL KSLALGFHSM VIRALGGILA PIYFGALIDT TCIKWSTNNC GTRGSCR TY NSTSFSRVYL GLSSMLRVSS LVLYIILIYA MKKKYQEKDI NASENGSVMD EANLESLNKN KHFVPSAGAD SETHC

UniProtKB: Solute carrier organic anion transporter family member 1B1

-
Macromolecule #2: Sybody 5

MacromoleculeName: Sybody 5 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: synthetic construct (others)
Molecular weightTheoretical: 15.88551 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
GSSSQVQLVE SGGGLVQAGG SLRLSCAASG FPVNLSYMHW YRQAPGKERE WVAAISSWGW HTEYADSVKG RFTISRDNAK NTVYLQMNS LKPEDTAVYY CHVRVGRSYF GQGTQVSVSA GRAGEQKLIS EEDLNSAVDH HHHHH

-
Macromolecule #3: Cyclosporin A

MacromoleculeName: Cyclosporin A / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: synthetic construct (others)
Molecular weightTheoretical: 1.220625 KDa
SequenceString:
(DAL)(MLE)(MLE)(MVA)(BMT)(ABA)(SAR)(MLE)V(MLE) A

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: TFS FALCON 4i (4k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.6 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: INSILICO MODEL
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.41 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 38974
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

+
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