EMD-42618
Structure of NaDC3-DMS complex in Ci-Ci conformation
EMD-42618
Single-particle2.17 Å
![EMD-42618](https://www.ebi.ac.uk/emdb/images/entry/EMD-42618/400_42618.gif)
Map released: 25/12/2024
Last modified: 08/01/2025
Sample Organism:
Homo sapiens
Sample: Dimer of NaDC3 in complex with 2,3-DMS
Fitted models: 8uvf (Avg. Q-score: 0.635)
Deposition Authors: Li Y, Wang DN
,
Mindell JA
,
Rice WJ
,
Song J,
Mikusevic V,
Marden JJ,
Becerril A,
Kuang H,
Wang B
Sample: Dimer of NaDC3 in complex with 2,3-DMS
Fitted models: 8uvf (Avg. Q-score: 0.635)
Deposition Authors: Li Y, Wang DN
![](http://www.ebi.ac.uk/web_guidelines/images/logos/orcid/orcid_16x16.png)
![](http://www.ebi.ac.uk/web_guidelines/images/logos/orcid/orcid_16x16.png)
![](http://www.ebi.ac.uk/web_guidelines/images/logos/orcid/orcid_16x16.png)
Substrate translocation and inhibition in human dicarboxylate transporter NaDC3.
Li Y,
Song J,
Mikusevic V,
Marden JJ,
Becerril A,
Kuang H,
Wang B,
Rice WJ
,
Mindell JA
,
Wang DN
(2024) Nat Struct Mol Biol
![](http://www.ebi.ac.uk/web_guidelines/images/logos/orcid/orcid_16x16.png)
![](http://www.ebi.ac.uk/web_guidelines/images/logos/orcid/orcid_16x16.png)
![](http://www.ebi.ac.uk/web_guidelines/images/logos/orcid/orcid_16x16.png)
(2024) Nat Struct Mol Biol
Abstract:
The human high-affinity sodium-dicarboxylate cotransporter (NaDC3) imports various substrates into the cell as tricarboxylate acid cycle intermediates, lipid biosynthesis precursors and signaling molecules. Understanding the cellular signaling process and developing inhibitors require knowledge of the structural basis of the dicarboxylate specificity and inhibition mechanism of NaDC3. To this end, we determined the cryo-electron microscopy structures of NaDC3 in various dimers, revealing the protomer in three conformations: outward-open Co, outward-occluded Coo and inward-open Ci. A dicarboxylate is first bound and recognized in Co and how the substrate interacts with NaDC3 in Coo likely helps to further determine the substrate specificity. A phenylalanine from the scaffold domain interacts with the bound dicarboxylate in the Coo state and modulates the kinetic barrier to the transport domain movement. Structural comparison of an inhibitor-bound structure of NaDC3 to that of the sodium-dependent citrate transporter suggests ways for making an inhibitor that is specific for NaDC3.
The human high-affinity sodium-dicarboxylate cotransporter (NaDC3) imports various substrates into the cell as tricarboxylate acid cycle intermediates, lipid biosynthesis precursors and signaling molecules. Understanding the cellular signaling process and developing inhibitors require knowledge of the structural basis of the dicarboxylate specificity and inhibition mechanism of NaDC3. To this end, we determined the cryo-electron microscopy structures of NaDC3 in various dimers, revealing the protomer in three conformations: outward-open Co, outward-occluded Coo and inward-open Ci. A dicarboxylate is first bound and recognized in Co and how the substrate interacts with NaDC3 in Coo likely helps to further determine the substrate specificity. A phenylalanine from the scaffold domain interacts with the bound dicarboxylate in the Coo state and modulates the kinetic barrier to the transport domain movement. Structural comparison of an inhibitor-bound structure of NaDC3 to that of the sodium-dependent citrate transporter suggests ways for making an inhibitor that is specific for NaDC3.