[English] 日本語
Yorodumi
- EMDB-31558: Structure of human SGLT2-MAP17 complex bound with empagliflozin -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-31558
TitleStructure of human SGLT2-MAP17 complex bound with empagliflozin
Map datapostprocessed map reboxed to 100
Sample
  • Complex: human soluble guanylate cyclase
    • Protein or peptide: Sodium/glucose cotransporter 2
    • Protein or peptide: PDZK1-interacting protein 1
  • Ligand: PALMITIC ACID
  • Ligand: (2S,3R,4R,5S,6R)-2-[4-chloranyl-3-[[4-[(3S)-oxolan-3-yl]oxyphenyl]methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol
Function / homology
Function and homology information


low-affinity D-glucose:sodium symporter activity / Defective SLC5A2 causes renal glucosuria (GLYS1) / alpha-glucoside transport / alpha-glucoside transmembrane transporter activity / D-glucose:sodium symporter activity / hexose transmembrane transport / renal D-glucose absorption / D-glucose import across plasma membrane / Cellular hexose transport / D-glucose transmembrane transporter activity ...low-affinity D-glucose:sodium symporter activity / Defective SLC5A2 causes renal glucosuria (GLYS1) / alpha-glucoside transport / alpha-glucoside transmembrane transporter activity / D-glucose:sodium symporter activity / hexose transmembrane transport / renal D-glucose absorption / D-glucose import across plasma membrane / Cellular hexose transport / D-glucose transmembrane transporter activity / sodium ion import across plasma membrane / sodium ion transport / carbohydrate metabolic process / apical plasma membrane / extracellular exosome / metal ion binding / membrane / plasma membrane
Similarity search - Function
PDZK1-interacting protein 1/SMIM24 / Membrane-associated protein 117 kDa, PDZK1-interacting protein 1 / Sodium:solute symporter family signature 2. / Sodium:solute symporter family signature 1. / Sodium/solute symporter, conserved site / Sodium/solute symporter / Sodium/glucose symporter superfamily / Sodium:solute symporter family / Sodium:solute symporter family profile.
Similarity search - Domain/homology
Sodium/glucose cotransporter 2 / PDZK1-interacting protein 1
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.95 Å
AuthorsChen L / Niu Y / Liu R
Funding support China, 3 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)91957201 China
National Natural Science Foundation of China (NSFC)31821091 China
National Natural Science Foundation of China (NSFC)31870833 China
CitationJournal: 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
DepositionJul 21, 2021-
Header (metadata) releaseOct 27, 2021-
Map releaseOct 27, 2021-
UpdateOct 26, 2022-
Current statusOct 26, 2022Processing site: PDBj / Status: Released

-
Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.02
  • Imaged by UCSF Chimera
  • Download
  • Surface view colored by height
  • Surface level: 0.02
  • Imaged by UCSF Chimera
  • Download
  • Surface view with fitted model
  • Atomic models: PDB-7vsi
  • Surface level: 0.02
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_31558.png

Downloads & links

-
Map

FileDownload / File: emd_31558.map.gz / Format: CCP4 / Size: 3.8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationpostprocessed map reboxed to 100
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.82 Å/pix.
x 100 pix.
= 82.1 Å		0.82 Å/pix.
x 100 pix.
= 82.1 Å		0.82 Å/pix.
x 100 pix.
= 82.1 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.821 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.02 / Movie #1: 0.02
Minimum - Maximum-0.048331663 - 0.09370973
Average (Standard dev.)0.0054411343 (±0.00966997)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions100100100
Spacing100100100
CellA=B=C: 82.1 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z0.8210.8210.821
M x/y/z100100100
origin x/y/z0.0000.0000.000
length x/y/z82.10082.10082.100
α/β/γ90.00090.00090.000
start NX/NY/NZ000
NX/NY/NZ240240240
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS100100100
D min/max/mean-0.0480.0940.005

-
Supplemental data

-
Additional map: refined map from relion

Fileemd_31558_additional_1.map
Annotationrefined map from relion
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : human soluble guanylate cyclase

EntireName: human soluble guanylate cyclase
Components
  • Complex: human soluble guanylate cyclase
    • Protein or peptide: Sodium/glucose cotransporter 2
    • Protein or peptide: PDZK1-interacting protein 1
  • Ligand: PALMITIC ACID
  • Ligand: (2S,3R,4R,5S,6R)-2-[4-chloranyl-3-[[4-[(3S)-oxolan-3-yl]oxyphenyl]methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol

-
Supramolecule #1: human soluble guanylate cyclase

SupramoleculeName: human soluble guanylate cyclase / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Homo sapiens (human)
Recombinant expressionOrganism: Homo sapiens (human)

-
Macromolecule #1: Sodium/glucose cotransporter 2

MacromoleculeName: Sodium/glucose cotransporter 2 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 72.949414 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: 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

MacromoleculeName: PDZK1-interacting protein 1 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 5.937134 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
MSALSLLILG LLTAVPPASC QQGLGNLQPW MQGLIAVAVF LVLVAIAFAV NHFWCQ

-
Macromolecule #3: PALMITIC ACID

MacromoleculeName: PALMITIC ACID / type: ligand / ID: 3 / Number of copies: 2 / Formula: PLM
Molecular weightTheoretical: 256.424 Da
Chemical component information

ChemComp-PLM:
PALMITIC ACID

-
Macromolecule #4: (2S,3R,4R,5S,6R)-2-[4-chloranyl-3-[[4-[(3S)-oxolan-3-yl]oxyphenyl...

MacromoleculeName: (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
Molecular weightTheoretical: 450.909 Da
Chemical component information

ChemComp-7R3:
(2S,3R,4R,5S,6R)-2-[4-chloranyl-3-[[4-[(3S)-oxolan-3-yl]oxyphenyl]methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol / medication*YM

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K2 QUANTUM (4k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

-
Image processing

Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.95 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 3.1) / Number images used: 36375
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more