+Open data
-Basic information
Entry | Database: PDB / ID: 7vsi | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Structure of human SGLT2-MAP17 complex bound with empagliflozin | ||||||||||||
Components |
| ||||||||||||
Keywords | TRANSPORT PROTEIN / glucose transporter / SGLT2 / SGLT | ||||||||||||
Function / homology | Function and homology information low-affinity glucose:sodium symporter activity / Defective SLC5A2 causes renal glucosuria (GLYS1) / alpha-glucoside transport / alpha-glucoside transmembrane transporter activity / glucose:sodium symporter activity / hexose transmembrane transport / D-glucose transmembrane transporter activity / Cellular hexose transport / renal glucose absorption / glucose import across plasma membrane ...low-affinity glucose:sodium symporter activity / Defective SLC5A2 causes renal glucosuria (GLYS1) / alpha-glucoside transport / alpha-glucoside transmembrane transporter activity / glucose:sodium symporter activity / hexose transmembrane transport / D-glucose transmembrane transporter activity / Cellular hexose transport / renal glucose absorption / glucose import across plasma membrane / sodium ion import across plasma membrane / sodium ion transport / carbohydrate metabolic process / apical plasma membrane / extracellular exosome / membrane / plasma membrane Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.95 Å | ||||||||||||
Authors | Chen, L. / Niu, Y. / Liu, R. | ||||||||||||
Funding support | China, 3items
| ||||||||||||
Citation | Journal: Nature / Year: 2022 Title: Structural basis of inhibition of the human SGLT2-MAP17 glucose transporter. Authors: Yange Niu / Rui Liu / Chengcheng Guan / Yuan Zhang / Zhixing Chen / Stefan Hoerer / Herbert Nar / Lei Chen / 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, ...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. | ||||||||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7vsi.cif.gz | 124.2 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb7vsi.ent.gz | 100.8 KB | Display | PDB format |
PDBx/mmJSON format | 7vsi.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7vsi_validation.pdf.gz | 954.8 KB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 7vsi_full_validation.pdf.gz | 963.1 KB | Display | |
Data in XML | 7vsi_validation.xml.gz | 28.6 KB | Display | |
Data in CIF | 7vsi_validation.cif.gz | 41.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/vs/7vsi ftp://data.pdbj.org/pub/pdb/validation_reports/vs/7vsi | HTTPS FTP |
-Related structure data
Related structure data | 31558MC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
#1: Protein | Mass: 72949.414 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: SLC5A2, SGLT2 / Production host: Homo sapiens (human) / References: UniProt: P31639 | ||||
---|---|---|---|---|---|
#2: Protein | Mass: 5937.134 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PDZK1IP1, MAP17 / Production host: Homo sapiens (human) / References: UniProt: Q13113 | ||||
#3: Chemical | #4: Chemical | ChemComp-7R3 / ( | Has ligand of interest | Y | |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: human SGLT2-MAP17 complex / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
EM software | Name: RELION / Version: 3.1 / Category: 3D reconstruction |
---|---|
CTF correction | Type: NONE |
3D reconstruction | Resolution: 2.95 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 36375 / Symmetry type: POINT |