Summary for 9J5Z
| Entry DOI | 10.2210/pdb9j5z/pdb |
| EMDB information | 61157 |
| Descriptor | Solute carrier family 22 member 12, verinurad (2 entities in total) |
| Functional Keywords | inhibitor, complex, membrane protein |
| Biological source | Rattus norvegicus (Norway rat) |
| Total number of polymer chains | 1 |
| Total formula weight | 60581.65 |
| Authors | |
| Primary citation | Fan, J.,Xie, W.,Ke, H.,Zhang, J.,Wang, J.,Wang, H.,Guo, N.,Bai, Y.,Lei, X. Structural Basis for Inhibition of Urate Reabsorption in URAT1. Jacs Au, 5:1308-1319, 2025 Cited by PubMed Abstract: The urate transporter 1 (URAT1) is the primary urate transporter in the kidney responsible for urate reabsorption and, therefore, is crucial for urate homeostasis. Hyperuricemia causes the common human disease gout and other pathological consequences. Inhibition of urate reabsorption through URAT1 has been shown as a promising strategy in alleviating hyperuricemia, and clinical and preclinical drug candidates targeting URAT1 are emerging. However, how small molecules inhibit URAT1 remains undefined, and the lack of accurate URAT1 complex structures hinders the development of better therapeutics. Here, we present cryoelectron microscopy structures of a humanized rat URAT1 bound with benzbromarone, lingdolinurad, and verinurad, elucidating the structural basis for drug recognition and inhibition. The three small molecules reside in the URAT1 central cavity with different binding modes, locking URAT1 in an inward-facing conformation. This study provides mechanistic insights into the drug modulation of URAT1 and sheds light on the rational design of potential URAT1-specific therapeutics for treating hyperuricemia. PubMed: 40151250DOI: 10.1021/jacsau.4c01188 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.5 Å) |
Structure validation
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