9JDV
Human URAT1 bound with Uric acid
Summary for 9JDV
| Entry DOI | 10.2210/pdb9jdv/pdb |
| EMDB information | 61399 |
| Descriptor | Solute carrier family 22 member 12, URIC ACID (3 entities in total) |
| Functional Keywords | urat1, transport protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 59839.94 |
| Authors | |
| Primary citation | Wu, C.,Zhang, C.,Jin, S.,Wang, J.J.,Dai, A.,Xu, J.,Zhang, H.,Yang, X.,He, X.,Yuan, Q.,Hu, W.,Xu, Y.,Wang, M.,Jiang, Y.,Yang, D.,Xu, H.E. Molecular mechanisms of urate transport by the native human URAT1 and its inhibition by anti-gout drugs. Cell Discov, 11:33-33, 2025 Cited by PubMed Abstract: Gout, a common and painful disease, stems from hyperuricemia, where elevated blood urate levels lead to urate crystal formation in joints and kidneys. The human urate transporter 1 (hURAT1) plays a critical role in urate homeostasis by facilitating urate reabsorption in the renal proximal tubule, making it a key target for gout therapy. Pharmacological inhibition of hURAT1 with drugs such as dotinurad, benzbromarone, lesinurad, and verinurad promotes urate excretion and alleviates gout symptoms. Here, we present cryo-electron microscopy structures of native hURAT1 bound with these anti-gout drugs in the inward-open state, and with urate in inward-open, outward-open, and occluded states. Complemented by mutagenesis and cell-based assays, these structures reveal the mechanisms of urate reabsorption and hURAT1 inhibition. Our findings elucidate the molecular basis of urate transport and anti-gout medication action and provide a structural framework for the rational design of next-generation therapies for hyperuricemia and gout. PubMed: 40169562DOI: 10.1038/s41421-025-00779-z PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.32 Å) |
Structure validation
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