[English] 日本語
Yorodumi
- PDB-9jdy: Human URAT1 bound with verinurad -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9jdy
TitleHuman URAT1 bound with verinurad
ComponentsSolute carrier family 22 member 12
KeywordsTRANSPORT PROTEIN / URAT1
Function / homology
Function and homology information


Defective SLC22A12 causes renal hypouricemia 1 (RHUC1) / Organic anion transport / renal urate salt excretion / urate transport / urate metabolic process / urate transmembrane transporter activity / organic anion transport / cellular homeostasis / monoatomic ion transport / PDZ domain binding ...Defective SLC22A12 causes renal hypouricemia 1 (RHUC1) / Organic anion transport / renal urate salt excretion / urate transport / urate metabolic process / urate transmembrane transporter activity / organic anion transport / cellular homeostasis / monoatomic ion transport / PDZ domain binding / brush border membrane / cellular response to insulin stimulus / apical plasma membrane / response to xenobiotic stimulus / extracellular exosome / membrane / plasma membrane
Similarity search - Function
Major facilitator superfamily / Major Facilitator Superfamily / 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 speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.23 Å
AuthorsWu, C. / Zhang, C. / Jin, S. / Wang, J.J. / Dai, A. / Jiang, Y. / Yang, D. / Xu, H.E.
Funding support China, 2items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)32130022 China
National Natural Science Foundation of China (NSFC)32301016 China
Citation
Journal: Cell Discov / Year: 2025
Title: Molecular mechanisms of urate transport by the native human URAT1 and its inhibition by anti-gout drugs.
Authors: Canrong Wu / Chao Zhang / Sanshan Jin / James Jiqi Wang / Antao Dai / Jiuyin Xu / Heng Zhang / Xuemei Yang / Xinheng He / Qingning Yuan / Wen Hu / Youwei Xu / Mingwei Wang / Yi Jiang / Dehua Yang / H Eric Xu /
Abstract: Gout, a common and painful disease, stems from hyperuricemia, where elevated blood urate levels lead to urate crystal formation in joints and kidneys. The human urate transporter 1 (hURAT1) plays a ...Gout, a common and painful disease, stems from hyperuricemia, where elevated blood urate levels lead to urate crystal formation in joints and kidneys. The human urate transporter 1 (hURAT1) plays a critical role in urate homeostasis by facilitating urate reabsorption in the renal proximal tubule, making it a key target for gout therapy. Pharmacological inhibition of hURAT1 with drugs such as dotinurad, benzbromarone, lesinurad, and verinurad promotes urate excretion and alleviates gout symptoms. Here, we present cryo-electron microscopy structures of native hURAT1 bound with these anti-gout drugs in the inward-open state, and with urate in inward-open, outward-open, and occluded states. Complemented by mutagenesis and cell-based assays, these structures reveal the mechanisms of urate reabsorption and hURAT1 inhibition. Our findings elucidate the molecular basis of urate transport and anti-gout medication action and provide a structural framework for the rational design of next-generation therapies for hyperuricemia and gout.
#1: Journal: Biorxiv / Year: 2024
Title: Molecular mechanisms of uric acid transport by the native human URAT1 and its inhibition by anti-gout drugs
Authors: Wu, C. / Zhang, C. / Jin, S. / Wang, J.J. / Dai, A. / Xu, J. / Zhang, H. / Yang, X. / He, X. / Yuan, Q. / Hu, W. / Xu, Y. / Wang, M. / Jiang, Y. / Yang, D. / Xu, H.E.
History
DepositionSep 1, 2024Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Oct 16, 2024Provider: repository / Type: Initial release
Revision 2.0Oct 23, 2024Group: Advisory / Atomic model ...Advisory / Atomic model / Data collection / Derived calculations / Refinement description / Structure summary
Category: atom_site / audit_author ...atom_site / audit_author / em_admin / em_imaging / em_software / pdbx_modification_feature / pdbx_unobs_or_zero_occ_atoms / pdbx_validate_close_contact / pdbx_validate_torsion / refine_ls_restr / struct_conf / struct_conn
Item: _em_admin.last_update / _em_imaging.microscope_model / Description: Model completeness / Provider: author / Type: Coordinate replacement
Revision 2.1Nov 6, 2024Group: Data collection / Category: em_admin / Item: _em_admin.last_update
Revision 2.2Apr 16, 2025Group: Data collection / Database references / Category: citation / citation_author / em_admin / Item: _em_admin.last_update

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Solute carrier family 22 member 12
hetero molecules


Theoretical massNumber of molelcules
Total (without water)60,0202
Polymers59,6721
Non-polymers3481
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

-
Components

#1: Protein Solute carrier family 22 member 12 / Organic anion transporter 4-like protein / Renal-specific transporter / RST / Urate anion exchanger ...Organic anion transporter 4-like protein / Renal-specific transporter / RST / Urate anion exchanger 1 / URAT1 / Urate:anion antiporter SLC22A12


Mass: 59671.828 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: SLC22A12, OATL4, URAT1, UNQ6453/PRO34004 / Production host: Homo sapiens (human) / References: UniProt: Q96S37
#2: Chemical ChemComp-A1AIJ / verinurad / 2-{[(3P)-3-(4-cyanonaphthalen-1-yl)pyridin-4-yl]sulfanyl}-2-methylpropanoic acid


Mass: 348.418 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H16N2O2S / Feature type: SUBJECT OF INVESTIGATION
Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: human uric acid transportor 1 with verinurad / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company
MicroscopyModel: FEI TALOS ARCTICA
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 5000 nm / Nominal defocus min: 1200 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: FEI FALCON I (4k x 4k)

-
Processing

CTF correctionType: PHASE FLIPPING ONLY
3D reconstructionResolution: 3.23 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 189878 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0023407
ELECTRON MICROSCOPYf_angle_d0.4514654
ELECTRON MICROSCOPYf_dihedral_angle_d16.994465
ELECTRON MICROSCOPYf_chiral_restr0.035544
ELECTRON MICROSCOPYf_plane_restr0.003576

+
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