9J73
Cryo-EM structure of URAT1 in complex with benzbromarone
Summary for 9J73
| Entry DOI | 10.2210/pdb9j73/pdb |
| EMDB information | 61192 |
| Descriptor | Solute carrier family 22 member 12, [3,5-bis(bromanyl)-4-oxidanyl-phenyl]-(2-ethyl-1-benzofuran-3-yl)methanone (2 entities in total) |
| Functional Keywords | protein structure, structural protein, transport protein |
| Biological source | Rattus norvegicus (Norway rat) |
| Total number of polymer chains | 1 |
| Total formula weight | 60675.36 |
| Authors | |
| Primary citation | Yu, Z.,Hu, T.,Su, J.,Zhao, J.,Li, R.,Ma, Q.,Chen, Q.,Bai, Q.,Dong, Y.,Yuan, P.,Li, N.,Zhang, X.C.,Zhao, Y. Molecular mechanism of drug inhibition of URAT1. Nat Commun, 16:6551-6551, 2025 Cited by PubMed Abstract: Hyperuricemia, characterized by elevated serum urate levels, is a key factor in the pathogenesis of gout. URAT1 is essential for renal urate reabsorption and has emerged as a critical therapeutic target for managing hyperuricemia. However, the precise transport mechanism and the inhibitory effects of uricosuric drugs on URAT1 remain unclear. Here, we present structures of the double-mutant rat homolog of URAT1 in complex with its substrate urate, and the clinical drugs benzbromarone, lesinurad, verinurad, and sulfinpyrazone. The urate-bound structure elucidates key residues involved in recognizing urate, while the structures bound with drugs clearly demonstrate the distinct binding mode of each drug with URAT1. These drugs stabilize URAT1's inward-facing state, blocking conformational transitions. Additionally, critical interactions essential for its conformational transition are identified. These findings provide a molecular framework for understanding the physiological function of URAT1 and for developing more efficacious therapies to treat hyperuricemia. PubMed: 40670375DOI: 10.1038/s41467-025-61226-x PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.5 Å) |
Structure validation
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