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- EMDB-53481: Cryo-EM structure of rat SLCO2A1 bound to zafirlukast. -

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Basic information

Entry
Database: EMDB / ID: EMD-53481
TitleCryo-EM structure of rat SLCO2A1 bound to zafirlukast.
Map data
Sample
  • Complex: SLCO2A1 protein in detergent-lipid micelle with zafirlukast drug.
    • Protein or peptide: Solute carrier organic anion transporter family member 2A1
  • Ligand: zafirlukast
  • Ligand: CHOLESTEROL HEMISUCCINATE
KeywordsOATP2A1 / plasma membrane localised / prostaglandin transporter / PGT / major facilitator superfamily. / MEMBRANE PROTEIN
Function / homology
Function and homology information


Organic anion transport by SLCO transporters / sodium-independent organic anion transport / : / prostaglandin transport / prostaglandin transmembrane transporter activity / basal plasma membrane / basolateral plasma membrane / lysosome
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 2A1
Similarity search - Component
Biological speciesRattus norvegicus (Norway rat)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.2 Å
AuthorsJoshi C / Newstead S
Funding support United Kingdom, 1 items
OrganizationGrant numberCountry
Wellcome Trust215519/Z/19/Z United Kingdom
CitationJournal: Nat Commun / Year: 2026
Title: Structural basis for prostaglandin and drug transport via SLCO2A1.
Authors: Chitra Joshi / Justin C Deme / Yoshinobu Nakamura / Wei-Tse Hsu / Jonathan D Goult / Takafumi Kato / Joanne L Parker / Philip C Biggin / Susan M Lea / Takeo Nakanishi / Simon Newstead /
Abstract: Organic anion-transporting polypeptide transporters (SLCO/OATPs) function as cellular gatekeepers, regulating intestinal absorption, hepatic and renal clearance, and the tissue distribution of drugs ...Organic anion-transporting polypeptide transporters (SLCO/OATPs) function as cellular gatekeepers, regulating intestinal absorption, hepatic and renal clearance, and the tissue distribution of drugs and metabolites in the human body. However, the mechanisms underlying substrate selection within the SLCO superfamily remain unclear, hampering efforts to rationalize the interaction of drugs and metabolites with these transporters. SLCO2A1 (also known as OATP2A1) is responsible for the distribution of eicosanoids, including prostaglandins (PGs) and thromboxanes, throughout the body, in addition to several families of nonsteroidal anti-inflammatory drugs (NSAIDs). Here, we present cryogenic electron microscopy structures of SLCO2A1 bound to endogenous PGs and to four widely prescribed medications for treating inflammation, chronic asthma, and Parkinson's disease (PD). Complementary molecular dynamics and in vivo cellular assays elucidate the molecular basis for PG and drug recognition. Our study reports essential mechanistic details that underpin substrate selection and subfamily adaptation within the broader SLCO superfamily of drug and metabolite transporters.
History
DepositionApr 24, 2025-
Header (metadata) releaseFeb 11, 2026-
Map releaseFeb 11, 2026-
UpdateApr 1, 2026-
Current statusApr 1, 2026Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

emd_53481.png

Downloads & links

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Map

FileDownload / File: emd_53481.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 300 pix.
= 249.6 Å		0.83 Å/pix.
x 300 pix.
= 249.6 Å		0.83 Å/pix.
x 300 pix.
= 249.6 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.832 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.25
Minimum - Maximum-0.66661596 - 1.2902924
Average (Standard dev.)-0.00013228561 (±0.030857308)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions300300300
Spacing300300300
CellA=B=C: 249.6 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_53481_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_53481_half_map_2.map
Projections & Slices
AxesZYX

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Histogram

Histogram (log scale)

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Sample components

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Entire : SLCO2A1 protein in detergent-lipid micelle with zafirlukast drug.

EntireName: SLCO2A1 protein in detergent-lipid micelle with zafirlukast drug.
Components
  • Complex: SLCO2A1 protein in detergent-lipid micelle with zafirlukast drug.
    • Protein or peptide: Solute carrier organic anion transporter family member 2A1
  • Ligand: zafirlukast
  • Ligand: CHOLESTEROL HEMISUCCINATE

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Supramolecule #1: SLCO2A1 protein in detergent-lipid micelle with zafirlukast drug.

SupramoleculeName: SLCO2A1 protein in detergent-lipid micelle with zafirlukast drug.
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Rattus norvegicus (Norway rat)

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Macromolecule #1: Solute carrier organic anion transporter family member 2A1

MacromoleculeName: Solute carrier organic anion transporter family member 2A1
type: protein_or_peptide / ID: 1
Details: Fusion protein: Avi tag (GLNDIFEAQKIEWHE) Linker as restriction site used for cloning (XhoI): 3'-SLCO2A1-Avitag-LEGG-5'
Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Rattus norvegicus (Norway rat)
Molecular weightTheoretical: 72.615117 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MGLLLKPGAR QGSGTSSVPD RRCPRSVFSN IKVFVLCHGL LQLCQLLYSA YFKSSLTTIE KRFGLSSSSS GLISSLNEIS NATLIIFIS YFGSRVNRPR MIGIGGLLLA AGAFVLTLPH FLSEPYQYTS TTDGNRSSFQ TDLCQKHFGA LPPSKCHSTV P DTHKETSS ...String:
MGLLLKPGAR QGSGTSSVPD RRCPRSVFSN IKVFVLCHGL LQLCQLLYSA YFKSSLTTIE KRFGLSSSSS GLISSLNEIS NATLIIFIS YFGSRVNRPR MIGIGGLLLA AGAFVLTLPH FLSEPYQYTS TTDGNRSSFQ TDLCQKHFGA LPPSKCHSTV P DTHKETSS LWGLMVVAQL LAGIGTVPIQ PFGISYVDDF AEPTNSPLYI SILFAIAVFG PAFGYLLGSV MLRIFVDYGR VD TATVNLS PGDPRWIGAW WLGLLISSGF LIVTSLPFFF FPRAMSRGAE RSVTAEETMQ TEEDKSRGSL MDFIKRFPRI FLR LLMNPL FMLVVLSQCT FSSVIAGLST FLNKFLEKQY GATAAYANFL IGAVNLPAAA LGMLFGGILM KRFVFPLQTI PRVA ATIIT ISMILCVPLF FMGCSTSAVA EVYPPSTSSS IHPQQPPACR RDCSCPDSFF HPVCGDNGVE YVSPCHAGCS STNTS SEAS KEPIYLNCSC VSGGSASAKT GSCPTSCAQL LLPSIFLISF AALIACISHN PLYMMVLRVV NQDEKSFAIG VQFLLM RLL AWLPAPSLYG LLIDSSCVRW NYLCSGRRGA CAYYDNDALR NRYLGLQMVY KALGTLLLFF ISWRMKKNRE YSLQENT SG LIGLNDIFEA QKIEWHELEG G

UniProtKB: Solute carrier organic anion transporter family member 2A1

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Macromolecule #2: zafirlukast

MacromoleculeName: zafirlukast / type: ligand / ID: 2 / Number of copies: 1 / Formula: ZLK
Molecular weightTheoretical: 575.675 Da
Chemical component information

ChemComp-ZLK:
zafirlukast / antagonist*YM

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Macromolecule #3: CHOLESTEROL HEMISUCCINATE

MacromoleculeName: CHOLESTEROL HEMISUCCINATE / type: ligand / ID: 3 / Number of copies: 1 / Formula: Y01
Molecular weightTheoretical: 486.726 Da
Chemical component information

ChemComp-Y01:
CHOLESTEROL HEMISUCCINATE

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.5
GridModel: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: PLASMA CLEANING
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277.15 K / Instrument: FEI VITROBOT MARK II

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: TFS FALCON 4i (4k x 4k) / Number grids imaged: 4 / Number real images: 15947 / Average exposure time: 1.5 sec. / Average electron dose: 32.8 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.4 µm / Nominal defocus min: 1.0 µm
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Particle selectionNumber selected: 11211159
CTF correctionSoftware - Name: SIMPLE (ver. 3.0) / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionAlgorithm: FOURIER SPACE / Resolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF
Software:
Namedetails
cryoSPARC (ver. 4.5.3)
RELION (ver. 3.1.)Bayesian Polishing

Number images used: 146876
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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Atomic model buiding 1

Initial modelPDB ID:

0-f1


Chain - Source name: AlphaFold / Chain - Initial model type: in silico model
RefinementSpace: REAL / Protocol: RIGID BODY FIT
Output model

PDB-9r07:
Cryo-EM structure of rat SLCO2A1 bound to zafirlukast.

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