7VSI

Structure of human SGLT2-MAP17 complex bound with empagliflozin

「7FEN」から置き換えられました

7VSI の概要

• エントリーDOI: 10.2210/pdb7vsi/pdb
• EMDBエントリー: 31558
• 分子名称: Sodium/glucose cotransporter 2, PDZK1-interacting protein 1, PALMITIC ACID, ... (4 entities in total)
• 機能のキーワード: glucose transporter, sglt2, sglt, transport protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 79850.31

構造登録者

Chen, L.,Niu, Y.,Liu, R. (登録日: 2021-10-26, 公開日: 2021-12-15, 最終更新日: 2024-11-13)

主引用文献

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

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: 34880493
DOI: 10.1038/s41586-021-04212-9

実験手法

ELECTRON MICROSCOPY (2.95 Å)