A5111325224- Gout, Hyperuricemia, Uric Acid
- Inflammatory mediators and NSAID effects
- Receptor Mechanisms and Signaling
- Organic Chemistry Cycloaddition Reactions
- Biochemical and Molecular Research
- Neuropeptides and Animal Physiology
- Synthesis and biological activity
- Metabolism and Genetic Disorders
- Case Reports on Hematomas
ShanghaiTech University
2024-2025
Shanghai Institute of Materia Medica
2024-2025
Chinese Academy of Sciences
2024-2025
University of Chinese Academy of Sciences
2024-2025
Prostaglandin E 2 (PGE ) mediates diverse physiological processes through four G protein–coupled receptor subtypes (EP1–EP4). While structures of EP2, EP3, and EP4 have been determined, the structural basis for PGE recognition activation EP1 subtype has remained elusive due to its inherent instability. Here, we present cryoelectron microscopy structure human in complex with heterotrimeric Gq protein at 2.55 Å resolution, completing characterization EP family. Our reveals a unique binding...
Abstract Gout, a common and painful disease, stems from hyperuricemia, where elevated blood urate levels lead to crystal formation in joints kidneys. The human transporter 1 (hURAT1) plays critical role homeostasis by facilitating reabsorption the renal proximal tubule, making it key target for gout therapy. Pharmacological inhibition of hURAT1 with drugs such as dotinurad, benzbromarone, lesinurad, verinurad promotes excretion alleviates symptoms. Here, we present cryo-electron microscopy...
The prostaglandin D2 receptor 1 (DP1), a rhodopsin-like Class A GPCR, orchestrates critical physiological and pathological processes, ranging from sleep regulation to inflammatory responses cardiovascular function. Despite its therapeutic significance, structural insights into DP1 activation mechanisms have remained elusive. Here, using cryoelectron microscopy (cryo-EM), we determined high-resolution structures of human in both inactive active states, with the latter captured complex...
Gout, a common and painful disease, stems from hyperuricemia, where elevated blood uric acid levels lead to urate crystal formation in joints kidneys. The human transporter 1 (hURAT1) plays critical role homeostasis by facilitating reabsorption the renal proximal tubule, making it key target for gout therapy. Pharmacological inhibition of hURAT1 with drugs such as dotinurad, benzbromarone, lesinurad, verinurad promotes excretion alleviates symptoms. Here we present cryo-electron microscopy...
Prostaglandin D2 receptor 2 (DP2) is an important anti-inflammatory and antiallergic drug target. While inactive DP2 structures are known, its activation mechanisms biased signaling remain unclear. Here, we report cryo-EM of apo DP2–Gi complex, a complex bound to the endogenous ligand D (PGD ), indomethacin, arrestin-biased ligand, at resolutions 2.5 Å, 2.8Å, 2.3 respectively. These reveal distinct binding pose PGD indomethacin provide key insights into transducer coupling. Combining...
Abstract Prostaglandin E2 (PGE2) signaling through EP2 and EP4 receptors plays a crucial role in inflammation, pain, cancer progression. Selective dual antagonists of these have shown promising therapeutic potential. However, the structural basis for their binding modes selectivity remained unclear. Here, we present cryo-EM structures human complex with selective PF-04418948 grapiprant, respectively, as well antagonist TG6-129. These reveal distinct pockets interaction networks that govern...