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Molecular mechanisms of urate transport by the native human URAT1 and its inhibition by anti-gout drugs
by
Yuan, Qingning
, He, Xinheng
, Wu, Canrong
, Xu, H. Eric
, Jiang, Yi
, Yang, Dehua
, Wang, James Jiqi
, Jin, Sanshan
, Wang, Mingwei
, Zhang, Chao
, Dai, Antao
, Yang, Xuemei
, Hu, Wen
, Zhang, Heng
, Xu, Youwei
, Xu, Jiuyin
in
631/337/2569
/ 631/535/1258/1259
/ Biomedical and Life Sciences
/ Blood levels
/ Cell Biology
/ Cell Culture
/ Cell Cycle Analysis
/ Cell Physiology
/ Chemical bonds
/ Drugs
/ Electron microscopy
/ Gout
/ Homeostasis
/ Hyperuricemia
/ Kidneys
/ Life Sciences
/ Molecular modelling
/ Mutagenesis
/ Reabsorption
/ Rheumatism
/ Stem Cells
/ Uric acid
2025
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Molecular mechanisms of urate transport by the native human URAT1 and its inhibition by anti-gout drugs
by
Yuan, Qingning
, He, Xinheng
, Wu, Canrong
, Xu, H. Eric
, Jiang, Yi
, Yang, Dehua
, Wang, James Jiqi
, Jin, Sanshan
, Wang, Mingwei
, Zhang, Chao
, Dai, Antao
, Yang, Xuemei
, Hu, Wen
, Zhang, Heng
, Xu, Youwei
, Xu, Jiuyin
in
631/337/2569
/ 631/535/1258/1259
/ Biomedical and Life Sciences
/ Blood levels
/ Cell Biology
/ Cell Culture
/ Cell Cycle Analysis
/ Cell Physiology
/ Chemical bonds
/ Drugs
/ Electron microscopy
/ Gout
/ Homeostasis
/ Hyperuricemia
/ Kidneys
/ Life Sciences
/ Molecular modelling
/ Mutagenesis
/ Reabsorption
/ Rheumatism
/ Stem Cells
/ Uric acid
2025
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Molecular mechanisms of urate transport by the native human URAT1 and its inhibition by anti-gout drugs
by
Yuan, Qingning
, He, Xinheng
, Wu, Canrong
, Xu, H. Eric
, Jiang, Yi
, Yang, Dehua
, Wang, James Jiqi
, Jin, Sanshan
, Wang, Mingwei
, Zhang, Chao
, Dai, Antao
, Yang, Xuemei
, Hu, Wen
, Zhang, Heng
, Xu, Youwei
, Xu, Jiuyin
in
631/337/2569
/ 631/535/1258/1259
/ Biomedical and Life Sciences
/ Blood levels
/ Cell Biology
/ Cell Culture
/ Cell Cycle Analysis
/ Cell Physiology
/ Chemical bonds
/ Drugs
/ Electron microscopy
/ Gout
/ Homeostasis
/ Hyperuricemia
/ Kidneys
/ Life Sciences
/ Molecular modelling
/ Mutagenesis
/ Reabsorption
/ Rheumatism
/ Stem Cells
/ Uric acid
2025
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Molecular mechanisms of urate transport by the native human URAT1 and its inhibition by anti-gout drugs
Journal Article
Molecular mechanisms of urate transport by the native human URAT1 and its inhibition by anti-gout drugs
2025
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Overview
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.
Publisher
Springer Nature Singapore,Springer Nature B.V,Nature Publishing Group
Subject
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