ArticleNature communications2025
Mechanism of substrate recognition and release of human SGLT2.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- SGLT2 inhibitors: mechanisms, physiology and pharmacology, and clinical applications.Molecular biomedicine · 2026Review
- Structural basis for multivitamin recognition and transport by human SMVT.Nature communications · 2026Article
- Stacked ensemble learning and in-silico profiling reveal dual DPP-IV and SGLT2 inhibitors from Moringa oleifera metabolites.Scientific reports · 2026Article
- Computational Discovery of Novel SGLT2 Inhibitors from Eight Selected Medicine Food Homology Herbs Using a Multi-Stage Virtual Screening Pipeline.Pharmaceuticals (Basel, Switzerland) · 2026Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Glucose is a vital energy source essential for life and human health. Sodium-glucose cotransporter 2 (SGLT2) is a sodium-glucose symporter that utilizes the electrochemical gradient of sodium to reabsorb glucose from kidney filtrate back into circulation. SGLT2 plays a crucial role in maintaining blood glucose homeostasis and is an important drug target for type 2 diabetes. Despite its significance, the mechanisms by which SGLT2 recognizes and releases substrates during its transport cycle remain largely unknown. Here, we present structures of human SGLT2 in complex with a glucose analogue in the occluded conformation at 2.6 Å resolution, revealing a detailed hydrogen bonding network at the substrate binding site that governs substrate recognition. Additionally, structures of SGLT2 in both the substrate-bound inward-facing conformation and the substrate-free inward-facing conformations illustrate the structural changes that occur during substrate release into cytosol. Our structural analysis, combined with mutagenesis results, identifies specific polar interactions that are essential for maintaining the outer and inner gates in their closed conformations.
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Registered trials
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