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- EMDB-31558: Structure of human SGLT2-MAP17 complex bound with empagliflozin -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-31558 | ||||||||||||
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Title | Structure of human SGLT2-MAP17 complex bound with empagliflozin | ||||||||||||
![]() | postprocessed map reboxed to 100 | ||||||||||||
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Function / homology | ![]() 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 | ![]() | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.95 Å | ||||||||||||
![]() | Chen L / Niu Y / Liu R | ||||||||||||
Funding support | ![]()
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![]() | ![]() 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 |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 3.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 14.4 KB 14.4 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 10 KB | Display | ![]() |
Images | ![]() | 68.5 KB | ||
Others | ![]() | 65.1 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7vsiMC ![]() 7fen M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | postprocessed map reboxed to 100 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.821 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: refined map from relion
File | emd_31558_additional_1.map | ||||||||||||
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Annotation | refined map from relion | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : human soluble guanylate cyclase
Entire | Name: human soluble guanylate cyclase |
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Components |
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-Supramolecule #1: human soluble guanylate cyclase
Supramolecule | Name: human soluble guanylate cyclase / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
-Macromolecule #1: Sodium/glucose cotransporter 2
Macromolecule | Name: Sodium/glucose cotransporter 2 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 72.949414 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MEEHTEAGSA PEMGAQKALI DNPADILVIA AYFLLVIGVG LWSMCRTNRG TVGGYFLAGR SMVWWPVGAS LFASNIGSGH FVGLAGTGA ASGLAVAGFE WNALFVVLLL GWLFAPVYLT AGVITMPQYL RKRFGGRRIR LYLSVLSLFL YIFTKISVDM F SGAVFIQQ ...String: MEEHTEAGSA PEMGAQKALI DNPADILVIA AYFLLVIGVG LWSMCRTNRG TVGGYFLAGR SMVWWPVGAS LFASNIGSGH FVGLAGTGA ASGLAVAGFE WNALFVVLLL GWLFAPVYLT AGVITMPQYL RKRFGGRRIR LYLSVLSLFL YIFTKISVDM F SGAVFIQQ ALGWNIYASV IALLGITMIY TVTGGLAALM YTDTVQTFVI LGGACILMGY AFHEVGGYSG LFDKYLGAAT SL TVSEDPA VGNISSFCYR PRPDSYHLLR HPVTGDLPWP ALLLGLTIVS GWYWCSDQVI VQRCLAGKSL THIKAGCILC GYL KLTPMF LMVMPGMISR ILYPDEVACV VPEVCRRVCG TEVGCSNIAY PRLVVKLMPN GLRGLMLAVM LAALMSSLAS IFNS SSTLF TMDIYTRLRP RAGDRELLLV GRLWVVFIVV VSVAWLPVVQ AAQGGQLFDY IQAVSSYLAP PVSAVFVLAL FVPRV NEQG AFWGLIGGLL MGLARLIPEF SFGSGSCVQP SACPAFLCGV HYLYFAIVLF FCSGLLTLTV SLCTAPIPRK HLHRLV FSL RHSKEEREDL DADEQQGSSL PVQNGCPESA MEMNEPQAPA PSLFRQCLLW FCGMSRGGVG SPPPLTQEEA AAAARRL ED ISEDPSWARV VNLNALLMMA VAVFLWGFYA |
-Macromolecule #2: PDZK1-interacting protein 1
Macromolecule | Name: PDZK1-interacting protein 1 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 5.937134 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MSALSLLILG LLTAVPPASC QQGLGNLQPW MQGLIAVAVF LVLVAIAFAV NHFWCQ |
-Macromolecule #3: PALMITIC ACID
Macromolecule | Name: PALMITIC ACID / type: ligand / ID: 3 / Number of copies: 2 / Formula: PLM |
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Molecular weight | Theoretical: 256.424 Da |
Chemical component information | ![]() ChemComp-PLM: |
-Macromolecule #4: (2S,3R,4R,5S,6R)-2-[4-chloranyl-3-[[4-[(3S)-oxolan-3-yl]oxyphenyl...
Macromolecule | Name: (2S,3R,4R,5S,6R)-2-[4-chloranyl-3-[[4-[(3S)-oxolan-3-yl]oxyphenyl]methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol type: ligand / ID: 4 / Number of copies: 1 / Formula: 7R3 |
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Molecular weight | Theoretical: 450.909 Da |
Chemical component information | ![]() ChemComp-7R3: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |