9LHT
Cryo-EM structure of inhibitor E3 bound human urea transporter A2.
This is a non-PDB format compatible entry.
Summary for 9LHT
| Entry DOI | 10.2210/pdb9lht/pdb |
| EMDB information | 63105 |
| Descriptor | Urea transporter 2, 5-ethanoyl-~{N}-[3-(phenylsulfonylamino)phenyl]furan-2-carboxamide (2 entities in total) |
| Functional Keywords | urea transporter, membrane protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 3 |
| Total formula weight | 132565.80 |
| Authors | |
| Primary citation | Huang, S.M.,Cai, B.Y.,Liu, L.,Yang, L.J.,Li, Z.,Zhang, C.,Xiong, M.Y.,Zhang, H.,Li, Y.R.,Huang, Z.Z.,Sun, Y.,Yang, B.X.,Sun, J.P. Structural characterization of the urea transporter bound to the orally bioavailable inhibitor E3. Acta Pharmacol.Sin., 46:2989-2997, 2025 Cited by PubMed Abstract: Orally bioavailable inhibitors targeting the kidney urea transporter (UT) have the potential to serve as salt-sparing diuretics by employing a urea-selective diuretic mechanism of action distinct from that of diuretics targeting salt transporters. To elucidate the mechanism by which oral inhibitors interact with UTs, we solved the structure of a newly developed inhibitor, E3, with UT-A2 using cryo-electron microscopy. Through structural analysis and binding free energy calculations, we not only revealed the binding mode of E3 to UT-A2 but also clarified the structural basis by which E3 serves as a common competitive inhibitor of human, mouse and rat UT-A/UT-B. E3 exerts its inhibitory effect by competitively binding to the conserved Q-T-T-Q motif in the urea binding pockets of the transport channel. Moreover, we discovered that the BSBP region of UT can serve as a key region for enhancing the inhibitory potency of E3 with different UTs, which provides valuable structural insights for designing and modifying high-affinity UT inhibitors that act as diuretics. PubMed: 40523902DOI: 10.1038/s41401-025-01595-7 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3 Å) |
Structure validation
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