[English] 日本語
Yorodumi Papers
- Database of articles cited by EMDB/PDB/SASBDB data -

+
Search query

Keywords
Structure methods
Author
Journal
IF

-
Structure paper

TitleStructural basis of thiamine transport and drug recognition by SLC19A3.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 8542, Year 2024
Publish dateOct 2, 2024
AuthorsFlorian Gabriel / Lea Spriestersbach / Antonia Fuhrmann / Katharina E J Jungnickel / Siavash Mostafavi / Els Pardon / Jan Steyaert / Christian Löw /
PubMed AbstractThiamine (vitamin B) functions as an essential coenzyme in cells. Humans and other mammals cannot synthesise this vitamin de novo and thus have to take it up from their diet. Eventually, every cell ...Thiamine (vitamin B) functions as an essential coenzyme in cells. Humans and other mammals cannot synthesise this vitamin de novo and thus have to take it up from their diet. Eventually, every cell needs to import thiamine across its plasma membrane, which is mainly mediated by the two specific thiamine transporters SLC19A2 and SLC19A3. Loss of function mutations in either of these transporters lead to detrimental, life-threatening metabolic disorders. SLC19A3 is furthermore a major site of drug interactions. Many medications, including antidepressants, antibiotics and chemotherapeutics are known to inhibit this transporter, with potentially fatal consequences for patients. Despite a thorough functional characterisation over the past two decades, the structural basis of its transport mechanism and drug interactions has remained elusive. Here, we report seven cryo-electron microscopy (cryo-EM) structures of the human thiamine transporter SLC19A3 in complex with various ligands. Conformation-specific nanobodies enable us to capture different states of SLC19A3's transport cycle, revealing the molecular details of thiamine recognition and transport. We identify seven previously unknown drug interactions of SLC19A3 and present structures of the transporter in complex with the inhibitors fedratinib, amprolium and hydroxychloroquine. These data allow us to develop an understanding of the transport mechanism and ligand recognition of SLC19A3.
External linksNat Commun / PubMed:39358356 / PubMed Central
MethodsEM (single particle)
Resolution2.87 - 3.75 Å
Structure data

19716

8s4u

EMDB-19716, PDB-8s4u:
Cryo-EM structure of apo human SLC19A3 in outward-open state
Method: EM (single particle) / Resolution: 3.09 Å

19750

8s5u

EMDB-19750, PDB-8s5u:
Cryo-EM structure of thiamine-bound human SLC19A3 in outward-open state
Method: EM (single particle) / Resolution: 3.28 Å

19752

8s5w

EMDB-19752, PDB-8s5w:
Cryo-EM structure of fedratinib-bound human SLC19A3 in inward-open state
Method: EM (single particle) / Resolution: 3.05 Å

19753

8s5z

EMDB-19753, PDB-8s5z:
Cryo-EM structure of hydroxychloroquine-bound human SLC19A3 in inward-open state
Method: EM (single particle) / Resolution: 3.0 Å

19754

8s61

EMDB-19754, PDB-8s61:
Cryo-EM structure of thiamine-bound human SLC19A3 in inward-open state
Method: EM (single particle) / Resolution: 3.53 Å

19755

8s62

EMDB-19755, PDB-8s62:
Cryo-EM structure of amprolium-bound human SLC19A3 in inward-open state
Method: EM (single particle) / Resolution: 3.75 Å

51088

9g5k

EMDB-51088, PDB-9g5k:
Cryo-EM structure of apo human SLC19A3 in inward-open state
Method: EM (single particle) / Resolution: 2.87 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-VIB:
3-(4-AMINO-2-METHYL-PYRIMIDIN-5-YLMETHYL)-5-(2-HYDROXY-ETHYL)-4-METHYL-THIAZOL-3-IUM / medication*YM

ChemComp-2TA:
N-tert-butyl-3-{[5-methyl-2-({4-[2-(pyrrolidin-1-yl)ethoxy]phenyl}amino)pyrimidin-4-yl]amino}benzenesulfonamide / medication, anticancer*YM

PDB-1h5d:
X-ray induced reduction of horseradish peroxidase C1A Compound III (0-11% dose)

PDB-1h5c:
X-ray induced reduction of horseradish peroxidase C1A Compound III (100-200% dose)

Source
  • homo sapiens (human)
  • lama glama (llama)
KeywordsMEMBRANE PROTEIN / SLC19A3 / vitamin transporter / thiamine transporter / MFS fold / nanobody complex

+
About Yorodumi Papers

-
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 Papers

Database of articles cited by EMDB/PDB/SASBDB data

  • Database of articles cited by EMDB, PDB, and SASBDB entries
  • Using PubMed data

Related info.:EMDB / PDB / SASBDB / Yorodumi / EMN Papers / Changes in new EM Navigator and Yorodumi

Read more