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Title | Structural characterization of human urea transporters UT-A and UT-B and their inhibition. |
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Journal, issue, pages | Sci Adv, Vol. 9, Issue 39, Page eadg8229, Year 2023 |
Publish date | Sep 29, 2023 |
Authors | Gamma Chi / Larissa Dietz / Haiping Tang / Matthew Snee / Andreea Scacioc / Dong Wang / Gavin Mckinley / Shubhashish M M Mukhopadhyay / Ashley C W Pike / Rod Chalk / Nicola A Burgess-Brown / Jean-Pierre Timmermans / Wouter van Putte / Carol V Robinson / Katharina L Dürr / |
PubMed Abstract | In this study, we present the structures of human urea transporters UT-A and UT-B to characterize them at molecular level and to detail the mechanism of UT-B inhibition by its selective inhibitor, ...In this study, we present the structures of human urea transporters UT-A and UT-B to characterize them at molecular level and to detail the mechanism of UT-B inhibition by its selective inhibitor, UTB-14. High-resolution structures of both transporters establish the structural basis for the inhibitor's selectivity to UT-B, and the identification of multiple binding sites for the inhibitor will aid with the development of drug lead molecules targeting both transporters. Our study also discovers phospholipids associating with the urea transporters by combining structural observations, native MS, and lipidomics analysis. These insights improve our understanding of urea transporter function at a molecular level and provide a blueprint for a structure-guided design of therapeutics targeting these transporters. |
External links | Sci Adv / PubMed:37774028 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.6 - 3.0 Å |
Structure data | EMDB-16110, PDB-8blo: EMDB-16111: Map of Human Urea Transporter UT-A Collected with 0 and 30 Degree Tilts EMDB-16112, PDB-8blp: |
Chemicals | ChemComp-PLD: ChemComp-LMN: ChemComp-HOH: ChemComp-PTY: ChemComp-LMT: ChemComp-5D3: ChemComp-Y01: |
Source |
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Keywords | TRANSPORT PROTEIN / SLC14A2 / UT2 / UT-A / Urea Transporter / Inhibitor / Solute Carrier / SLC14A1 / UT1 / UT-B |