8Y66

Cryo-EM structure of human urate transporter GLUT9 bound to inhibitor apigenin

8Y66 の概要

• エントリーDOI: 10.2210/pdb8y66/pdb
• EMDBエントリー: 38968
• 分子名称: Solute carrier family 2, facilitated glucose transporter member 9, 5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one (2 entities in total)
• 機能のキーワード: glut9, inhibitor, apigenin, 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: 63485.33

構造登録者

Pan, X.J.,Shen, Z.L.,Xu, L.,Huang, G.X.Y. (登録日: 2024-02-01, 公開日: 2024-06-19)

主引用文献

Shen, Z.,Xu, L.,Wu, T.,Wang, H.,Wang, Q.,Ge, X.,Kong, F.,Huang, G.,Pan, X.
Structural basis for urate recognition and apigenin inhibition of human GLUT9.
Nat Commun, 15:5039-5039, 2024

PubMed Abstract: Urate, the physiological form of uric acid and a potent antioxidant in serum, plays a pivotal role in scavenging reactive oxygen species. Yet excessive accumulation of urate, known as hyperuricemia, is the primary risk factor for the development of gout. The high-capacity urate transporter GLUT9 represents a promising target for gout treatment. Here, we present cryo-electron microscopy structures of human GLUT9 in complex with urate or its inhibitor apigenin at overall resolutions of 3.5 Å and 3.3 Å, respectively. In both structures, GLUT9 exhibits an inward open conformation, wherein the substrate binding pocket faces the intracellular side. These structures unveil the molecular basis for GLUT9's substrate preference of urate over glucose, and show that apigenin acts as a competitive inhibitor by occupying the substrate binding site. Our findings provide critical information for the development of specific inhibitors targeting GLUT9 as potential therapeutics for gout and hyperuricemia.

PubMed: 38866775
DOI: 10.1038/s41467-024-49420-9

実験手法

ELECTRON MICROSCOPY (3.28 Å)