Mechanisms of urate transport and uricosuric drugs inhibition in human URAT1.

ABSTRACT: High urate levels in circulation lead to the accumulation of urate crystals in joints and ultimately inflammation and gout. The reabsorption process of urate in the kidney by the urate transporter URAT1 plays a pivotal role in controlling serum urate levels. Pharmacological inhibition of URAT1 by uricosuric drugs is a valid strategy for gout management. Despite the clinical significance of URAT1, its structural mechanism and dynamics remain incompletely understood. Here, we report the structures of human URAT1 (hURAT1) in complex with substrate urate or inhibitors benzbromarone and verinurad at resolution ranges from 3.0 to 3.3 Å. We observe urate in the central substrate-binding site of hURAT1 in the outward-facing conformation and urate is wrapped in the center of hURAT1 by five phenylal

SUBMITTER: Guo W 

PROVIDER: S-EPMC11811179 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature