[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

TitleStructure and inhibition mechanism of the human citrate transporter NaCT.
Journal, issue, pagesNature, Vol. 591, Issue 7848, Page 157-161, Year 2021
Publish dateFeb 17, 2021
AuthorsDavid B Sauer / Jinmei Song / Bing Wang / Jacob K Hilton / Nathan K Karpowich / Joseph A Mindell / William J Rice / Da-Neng Wang /
PubMed AbstractCitrate is best known as an intermediate in the tricarboxylic acid cycle of the cell. In addition to this essential role in energy metabolism, the tricarboxylate anion also acts as both a precursor ...Citrate is best known as an intermediate in the tricarboxylic acid cycle of the cell. In addition to this essential role in energy metabolism, the tricarboxylate anion also acts as both a precursor and a regulator of fatty acid synthesis. Thus, the rate of fatty acid synthesis correlates directly with the cytosolic concentration of citrate. Liver cells import citrate through the sodium-dependent citrate transporter NaCT (encoded by SLC13A5) and, as a consequence, this protein is a potential target for anti-obesity drugs. Here, to understand the structural basis of its inhibition mechanism, we determined cryo-electron microscopy structures of human NaCT in complexes with citrate or a small-molecule inhibitor. These structures reveal how the inhibitor-which binds to the same site as citrate-arrests the transport cycle of NaCT. The NaCT-inhibitor structure also explains why the compound selectively inhibits NaCT over two homologous human dicarboxylate transporters, and suggests ways to further improve the affinity and selectivity. Finally, the NaCT structures provide a framework for understanding how various mutations abolish the transport activity of NaCT in the brain and thereby cause epilepsy associated with mutations in SLC13A5 in newborns (which is known as SLC13A5-epilepsy).
External linksNature / PubMed:33597751 / PubMed Central
MethodsEM (single particle)
Resolution3.04 - 3.12 Å
Structure data

EMDB-22456, PDB-7jsj:
Structure of the NaCT-PF2 complex
Method: EM (single particle) / Resolution: 3.12 Å

EMDB-22457, PDB-7jsk:
Structure of the NaCT-Citrate complex
Method: EM (single particle) / Resolution: 3.04 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

ChemComp-X3M:
(2R)-2-[2-(4-tert-butylphenyl)ethyl]-2-hydroxybutanedioic acid

ChemComp-NA:
SODIUM ION / Sodium

ChemComp-CIT:
CITRIC ACID / Citric acid

Source
  • homo sapiens (human)
KeywordsBinding Sites / Brain / Carrier Proteins / Citric Acid / Cryoelectron Microscopy / Dicarboxylic Acid Transporters / Epilepsy / Humans / Malates / Models, Molecular / Mutation / PF-06649298 / Phenylbutyrates / Protein Multimerization / SLC13A5 protein, human / Sodium / Substrate Specificity / Symporters / citrate-binding transport protein / MEMBRANE PROTEIN / Transporter / Inhibitor

+
About Yorodumi Papers

-
News

-
Aug 12, 2020. New: Covid-19 info

New: Covid-19 info

  • 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. New: 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. (see PDBe EMDB page)
  • 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 at PDBe / 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. See below links for details.
  • 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

+
Jun 16, 2017. Omokage search with filter

Omokage search with filter

  • Result of Omokage search can be filtered by keywords and the database types

Related info.:Omokage search

Read more

-
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