Transport and inhibition mechanism of the human SGLT2-MAP17 glucose transporter.
Journal
Nature structural & molecular biology
ISSN: 1545-9985
Titre abrégé: Nat Struct Mol Biol
Pays: United States
ID NLM: 101186374
Informations de publication
Date de publication:
06 Dec 2023
06 Dec 2023
Historique:
received:
10
01
2023
accepted:
22
09
2023
medline:
7
12
2023
pubmed:
7
12
2023
entrez:
6
12
2023
Statut:
aheadofprint
Résumé
Sodium-glucose cotransporter 2 (SGLT2) is imporant in glucose reabsorption. SGLT2 inhibitors suppress renal glucose reabsorption, therefore reducing blood glucose levels in patients with type 2 diabetes. We and others have developed several SGLT2 inhibitors starting from phlorizin, a natural product. Using cryo-electron microscopy, we present the structures of human (h)SGLT2-MAP17 complexed with five natural or synthetic inhibitors. The four synthetic inhibitors (including canagliflozin) bind the transporter in the outward conformations, while phlorizin binds it in the inward conformation. The phlorizin-hSGLT2 interaction exhibits biphasic kinetics, suggesting that phlorizin alternately binds to the extracellular and intracellular sides. The Na
Identifiants
pubmed: 38057552
doi: 10.1038/s41594-023-01134-0
pii: 10.1038/s41594-023-01134-0
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023. The Author(s).
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