9JE0

Human URAT1 bound to benzbromarone

9JE0 の概要

• エントリーDOI: 10.2210/pdb9je0/pdb
• EMDBエントリー: 61403
• 分子名称: Solute carrier family 22 member 12, [3,5-bis(bromanyl)-4-oxidanyl-phenyl]-(2-ethyl-1-benzofuran-3-yl)methanone (3 entities in total)
• 機能のキーワード: urat1, transport protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 60095.91

構造登録者

Wu, C.,Zhang, C.,Jin, S.,Wang, J.J.,Dai, A.,Jiang, Y.,Yang, D.,Xu, H.E. (登録日: 2024-09-01, 公開日: 2024-10-16, 最終更新日: 2025-04-16)

主引用文献

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

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: 40169562
DOI: 10.1038/s41421-025-00779-z

実験手法

ELECTRON MICROSCOPY (3.23 Å)