+Open data
-Basic information
Entry | Database: PDB / ID: 7wit | ||||||
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Title | Structure of SUR1 in complex with mitiglinide | ||||||
Components | ATP-sensitive inward rectifier potassium channel 11,ATP-binding cassette sub-family C member 8 isoform X1 | ||||||
Keywords | MEMBRANE PROTEIN / SUR1 / KATP / channel / mitiglinide | ||||||
Function / homology | Function and homology information ATP sensitive Potassium channels / ATP-activated inward rectifier potassium channel activity / Regulation of insulin secretion / ABC-family proteins mediated transport / Ion homeostasis / inward rectifying potassium channel / sulfonylurea receptor activity / inward rectifier potassium channel activity / nervous system process / regulation of monoatomic ion transmembrane transport ...ATP sensitive Potassium channels / ATP-activated inward rectifier potassium channel activity / Regulation of insulin secretion / ABC-family proteins mediated transport / Ion homeostasis / inward rectifying potassium channel / sulfonylurea receptor activity / inward rectifier potassium channel activity / nervous system process / regulation of monoatomic ion transmembrane transport / ankyrin binding / response to ATP / potassium ion import across plasma membrane / ABC-type transporter activity / negative regulation of insulin secretion / regulation of membrane potential / potassium ion transport / glucose metabolic process / transmembrane transporter binding / membrane => GO:0016020 / response to xenobiotic stimulus / ATP binding / plasma membrane Similarity search - Function | ||||||
Biological species | Bos taurus (cattle) Mesocricetus auratus (golden hamster) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.21 Å | ||||||
Authors | Chen, L. / Wang, M.M. | ||||||
Funding support | China, 1items
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Citation | Journal: Front Pharmacol / Year: 2022 Title: Structural Insights Into the High Selectivity of the Anti-Diabetic Drug Mitiglinide. Authors: Mengmeng Wang / Jing-Xiang Wu / Lei Chen / Abstract: Mitiglinide is a highly selective fast-acting anti-diabetic drug that induces insulin secretion by inhibiting pancreatic K channels. However, how mitiglinide binds K channels remains unknown. Here, ...Mitiglinide is a highly selective fast-acting anti-diabetic drug that induces insulin secretion by inhibiting pancreatic K channels. However, how mitiglinide binds K channels remains unknown. Here, we show the cryo-EM structure of the SUR1 subunit complexed with mitiglinide. The structure reveals that mitiglinide binds inside the common insulin secretagogue-binding site of SUR1, which is surrounded by TM7, TM8, TM16, and TM17. Mitiglinide locks SUR1 in the NBD-separated inward-facing conformation. The detailed structural analysis of the mitiglinide-binding site uncovers the molecular basis of its high selectivity. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7wit.cif.gz | 209.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7wit.ent.gz | 152.7 KB | Display | PDB format |
PDBx/mmJSON format | 7wit.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7wit_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 7wit_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 7wit_validation.xml.gz | 39.3 KB | Display | |
Data in CIF | 7wit_validation.cif.gz | 58.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/wi/7wit ftp://data.pdbj.org/pub/pdb/validation_reports/wi/7wit | HTTPS FTP |
-Related structure data
Related structure data | 32535MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 159439.844 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: Fusion protein of potassium channel, linkers and Abcc8 Source: (gene. exp.) Bos taurus (cattle), (gene. exp.) Mesocricetus auratus (golden hamster) Gene: KCNJ11, Abcc8 / Production host: Homo sapiens (human) / References: UniProt: A2VDS4, UniProt: A0A1U8CME7 |
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#2: Chemical | ChemComp-ATP / |
#3: Chemical | ChemComp-9I0 / ( |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Sulfonylurea receptor 1 / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Source (natural) | Organism: Mesocricetus auratus (golden hamster) |
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 |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 3000 nm / Nominal defocus min: 1500 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: DIRECT ELECTRON DE-16 (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: NONE | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.21 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 82717 / Symmetry type: POINT | ||||||||||||||||||||||||
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