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-Structure paper
| タイトル | Substrate translocation and inhibition in human dicarboxylate transporter NaDC3. |
|---|---|
| ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 32, Issue 3, Page 502-512, Year 2025 |
| 掲載日 | 2024年12月2日 |
著者 | Yan Li / Jinmei Song / Vedrana Mikusevic / Jennifer J Marden / Alissa Becerril / Huihui Kuang / Bing Wang / William J Rice / Joseph A Mindell / Da-Neng Wang / ![]() |
| PubMed 要旨 | The human high-affinity sodium-dicarboxylate cotransporter (NaDC3) imports various substrates into the cell as tricarboxylate acid cycle intermediates, lipid biosynthesis precursors and signaling ...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 C, outward-occluded C and inward-open C. A dicarboxylate is first bound and recognized in C and how the substrate interacts with NaDC3 in C likely helps to further determine the substrate specificity. A phenylalanine from the scaffold domain interacts with the bound dicarboxylate in the C 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. |
リンク | Nat Struct Mol Biol / PubMed:39622972 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.09 - 2.92 Å |
| 構造データ | EMDB-42614, PDB-8uvb: EMDB-42615, PDB-8uvc: EMDB-42616, PDB-8uvd: EMDB-42617, PDB-8uve: EMDB-42618, PDB-8uvf: EMDB-42619, PDB-8uvg: EMDB-42620, PDB-8uvh: EMDB-42621, PDB-8uvi: |
| 化合物 | ![]() ChemComp-NA: ![]()
ChemComp-XKC: ![]() ChemComp-AKG: ![]() ChemComp-C14: ![]() ChemComp-3PE: ![]() ChemComp-CLR: ![]() ChemComp-SIN: ![]()
ChemComp-XKH: |
| 由来 |
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キーワード | TRANSPORT PROTEIN / Na(+)/citrate cotransporter(NaCT) / Solute carries / Elevator type alternating access / membrane protein / Na(+)/dicarboxylate cotransporter(NaDC3) |
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