Summary for 7VSI
| Entry DOI | 10.2210/pdb7vsi/pdb |
| EMDB information | 31558 |
| Descriptor | Sodium/glucose cotransporter 2, PDZK1-interacting protein 1, PALMITIC ACID, ... (4 entities in total) |
| Functional Keywords | glucose transporter, sglt2, sglt, transport protein |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 79850.31 |
| Authors | |
| Primary citation | Niu, Y.,Liu, R.,Guan, C.,Zhang, Y.,Chen, Z.,Hoerer, S.,Nar, H.,Chen, L. Structural basis of inhibition of the human SGLT2-MAP17 glucose transporter. Nature, 601:280-284, 2022 Cited by PubMed Abstract: Human sodium-glucose cotransporter 2 (hSGLT2) mediates the reabsorption of the majority of filtrated glucose in the kidney. Pharmacological inhibition of hSGLT2 by oral small-molecule inhibitors, such as empagliflozin, leads to enhanced excretion of glucose and is widely used in the clinic to manage blood glucose levels for the treatment of type 2 diabetes. Here we determined the cryogenic electron microscopy structure of the hSGLT2-MAP17 complex in the empagliflozin-bound state to an overall resolution of 2.95 Å. Our structure shows eukaryotic SGLT-specific structural features. MAP17 interacts with transmembrane helix 13 of hSGLT2. Empagliflozin occupies both the sugar-substrate-binding site and the external vestibule to lock hSGLT2 in an outward-open conformation, thus inhibiting the transport cycle. Our work provides a framework for understanding the mechanism of SLC5A family glucose transporters and also develops a foundation for the future rational design and optimization of new inhibitors targeting these transporters. PubMed: 34880493DOI: 10.1038/s41586-021-04212-9 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.95 Å) |
Structure validation
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