[English] 日本語
Yorodumi
- EMDB-61157: Cryo-EM Structure of URAT1 in Complex with Verinurad -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-61157
TitleCryo-EM Structure of URAT1 in Complex with Verinurad
Map data
Sample
  • Complex: Cryo-EM Structure of URAT1 in Complex with Verinurad
    • Protein or peptide: Solute carrier family 22 member 12
  • Ligand: verinurad
KeywordsInhibitor / complex / MEMBRANE PROTEIN
Function / homology
Function and homology information


Organic anion transport by SLC22 transporters / renal urate salt excretion / urate transport / urate metabolic process / urate transmembrane transporter activity / organic anion transport / monoatomic ion transport / PDZ domain binding / brush border membrane / cellular response to insulin stimulus ...Organic anion transport by SLC22 transporters / renal urate salt excretion / urate transport / urate metabolic process / urate transmembrane transporter activity / organic anion transport / monoatomic ion transport / PDZ domain binding / brush border membrane / cellular response to insulin stimulus / apical plasma membrane / response to xenobiotic stimulus / membrane / plasma membrane
Similarity search - Function
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 12
Similarity search - Component
Biological speciesRattus norvegicus (Norway rat)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.5 Å
AuthorsFan J / Lei X
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC) China
CitationJournal: JACS Au / Year: 2025
Title: Structural Basis for Inhibition of Urate Reabsorption in URAT1.
Authors: Junping Fan / Wenjun Xie / Han Ke / Jing Zhang / Jin Wang / Haijun Wang / Nianxin Guo / Yingjie Bai / Xiaoguang Lei /
Abstract: The urate transporter 1 (URAT1) is the primary urate transporter in the kidney responsible for urate reabsorption and, therefore, is crucial for urate homeostasis. Hyperuricemia causes the common ...The urate transporter 1 (URAT1) is the primary urate transporter in the kidney responsible for urate reabsorption and, therefore, is crucial for urate homeostasis. Hyperuricemia causes the common human disease gout and other pathological consequences. Inhibition of urate reabsorption through URAT1 has been shown as a promising strategy in alleviating hyperuricemia, and clinical and preclinical drug candidates targeting URAT1 are emerging. However, how small molecules inhibit URAT1 remains undefined, and the lack of accurate URAT1 complex structures hinders the development of better therapeutics. Here, we present cryoelectron microscopy structures of a humanized rat URAT1 bound with benzbromarone, lingdolinurad, and verinurad, elucidating the structural basis for drug recognition and inhibition. The three small molecules reside in the URAT1 central cavity with different binding modes, locking URAT1 in an inward-facing conformation. This study provides mechanistic insights into the drug modulation of URAT1 and sheds light on the rational design of potential URAT1-specific therapeutics for treating hyperuricemia.
History
DepositionAug 13, 2024-
Header (metadata) releaseFeb 26, 2025-
Map releaseFeb 26, 2025-
UpdateJul 23, 2025-
Current statusJul 23, 2025Processing site: PDBc / Status: Released

-
Structure visualization

Supplemental images

emd_61157.png

Downloads & links

-
Map

FileDownload / File: emd_61157.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.85 Å/pix.
x 320 pix.
= 272. Å		0.85 Å/pix.
x 320 pix.
= 272. Å		0.85 Å/pix.
x 320 pix.
= 272. Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.85 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.17
Minimum - Maximum-0.6974812 - 1.0562044
Average (Standard dev.)-0.00018363318 (±0.018380446)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 272.0 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #1

Fileemd_61157_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_61157_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Cryo-EM Structure of URAT1 in Complex with Verinurad

EntireName: Cryo-EM Structure of URAT1 in Complex with Verinurad
Components
  • Complex: Cryo-EM Structure of URAT1 in Complex with Verinurad
    • Protein or peptide: Solute carrier family 22 member 12
  • Ligand: verinurad

-
Supramolecule #1: Cryo-EM Structure of URAT1 in Complex with Verinurad

SupramoleculeName: Cryo-EM Structure of URAT1 in Complex with Verinurad / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Rattus norvegicus (Norway rat)

-
Macromolecule #1: Solute carrier family 22 member 12

MacromoleculeName: Solute carrier family 22 member 12 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Rattus norvegicus (Norway rat)
Molecular weightTheoretical: 60.233234 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MAFPELLDRV GGRGRFQLLQ AVALVTPILW VTTQSMLENF SAAVPHHRCW VPLLDNSTSQ ASIPGDFGRD VLLAVSIPPG PDQRPHQCL RFRQPQWQLI ESNTTATNWS DADTEPCEDG WVYDHSTFRS TIVTTWDLVC DSQALRPMAQ SIFLAGILVG A AVCGHASD ...String:
MAFPELLDRV GGRGRFQLLQ AVALVTPILW VTTQSMLENF SAAVPHHRCW VPLLDNSTSQ ASIPGDFGRD VLLAVSIPPG PDQRPHQCL RFRQPQWQLI ESNTTATNWS DADTEPCEDG WVYDHSTFRS TIVTTWDLVC DSQALRPMAQ SIFLAGILVG A AVCGHASD RFGRRRVLTW SYLLVSVSGT IAALMPTFPL YCLFRFLVAS AVAGVMMNTA SLLMEWTSAQ AGPLMMTLNA LG FSFGQVL TGSVAYGVRS WRMLQLAVSA PFFLFFVYSW WLPESARWLI TVGRLDQSLR ELQRVAAVNR RKAEADTLTV EVL RSAMQE EPNGNQAGAR LGTLLHTPGL RLRTFISMLC WFAFGFTFFG LALDLQALGS NIFLLQALIG IVDLPVKMGS LLLL SRLGR RLCQASSLVL PGLCILANIL VPREMGILRS SLAVLGLGSL GAAFTCVTIF SSELFPTVIR MTAVGLGQVA ARGGA ILGP LVRLLGVYGS WLPLLVYGVV PVLSGLAALL LPETKNLPLP DTIQDIQKQS VKKVTHDIAG GSVLKSARL

UniProtKB: Solute carrier family 22 member 12

-
Macromolecule #2: verinurad

MacromoleculeName: verinurad / type: ligand / ID: 2 / Number of copies: 1 / Formula: A1AIJ
Molecular weightTheoretical: 348.418 Da

-
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: GATAN K3 (6k 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: 2.0 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: OTHER / Details: AF2 model
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 60262
Initial angle assignmentType: RANDOM ASSIGNMENT
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