+Open data
-Basic information
Entry | Database: PDB / ID: 7r52 | ||||||
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Title | Crystal structure of human TLR8 in complex with Compound 2 | ||||||
Components | Toll-like receptor 8 | ||||||
Keywords | IMMUNE SYSTEM / TLR8 / Toll-like receptor | ||||||
Function / homology | Function and homology information Toll Like Receptor 7/8 (TLR7/8) Cascade / toll-like receptor 8 signaling pathway / negative regulation of interleukin-12 production / endolysosome membrane / positive regulation of innate immune response / Trafficking and processing of endosomal TLR / pattern recognition receptor activity / toll-like receptor signaling pathway / positive regulation of interferon-alpha production / immunoglobulin mediated immune response ...Toll Like Receptor 7/8 (TLR7/8) Cascade / toll-like receptor 8 signaling pathway / negative regulation of interleukin-12 production / endolysosome membrane / positive regulation of innate immune response / Trafficking and processing of endosomal TLR / pattern recognition receptor activity / toll-like receptor signaling pathway / positive regulation of interferon-alpha production / immunoglobulin mediated immune response / canonical NF-kappaB signal transduction / positive regulation of interferon-beta production / positive regulation of interleukin-1 beta production / positive regulation of interleukin-8 production / regulation of protein phosphorylation / response to virus / positive regulation of interleukin-6 production / cellular response to mechanical stimulus / double-stranded RNA binding / positive regulation of type II interferon production / signaling receptor activity / defense response to virus / single-stranded RNA binding / endosome membrane / inflammatory response / external side of plasma membrane / Golgi membrane / innate immune response / endoplasmic reticulum membrane / SARS-CoV-2 activates/modulates innate and adaptive immune responses / DNA binding / RNA binding / identical protein binding / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.943 Å | ||||||
Authors | Faller, M. / Zink, F. | ||||||
Funding support | 1items
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Citation | Journal: Acs Med.Chem.Lett. / Year: 2022 Title: Structure-Based Optimization of a Fragment-like TLR8 Binding Screening Hit to an In Vivo Efficacious TLR7/8 Antagonist. Authors: Betschart, C. / Faller, M. / Zink, F. / Hemmig, R. / Blank, J. / Vangrevelinghe, E. / Bourrel, M. / Glatthar, R. / Behnke, D. / Barker, K. / Heizmann, A. / Angst, D. / Nimsgern, P. / ...Authors: Betschart, C. / Faller, M. / Zink, F. / Hemmig, R. / Blank, J. / Vangrevelinghe, E. / Bourrel, M. / Glatthar, R. / Behnke, D. / Barker, K. / Heizmann, A. / Angst, D. / Nimsgern, P. / Jacquier, S. / Junt, T. / Zipfel, G. / Ruzzante, G. / Loetscher, P. / Limonta, S. / Hawtin, S. / Andre, C.B. / Boulay, T. / Feifel, R. / Knoepfel, T. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7r52.cif.gz | 590 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7r52.ent.gz | 490.5 KB | Display | PDB format |
PDBx/mmJSON format | 7r52.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/r5/7r52 ftp://data.pdbj.org/pub/pdb/validation_reports/r5/7r52 | HTTPS FTP |
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-Related structure data
Related structure data | 7r53C 7r54C 3w3gS S: Starting model for refinement 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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Unit cell |
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-Components
-Protein , 1 types, 2 molecules AB
#1: Protein | Mass: 92307.766 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TLR8, UNQ249/PRO286 / Production host: Drosophila melanogaster (fruit fly) / References: UniProt: Q9NR97 |
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-Sugars , 3 types, 18 molecules
#2: Polysaccharide | alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2- ...alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #3: Polysaccharide | Source method: isolated from a genetically manipulated source #4: Sugar | ChemComp-NAG / |
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-Non-polymers , 2 types, 217 molecules
#5: Chemical | #6: Water | ChemComp-HOH / | |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.54 Å3/Da / Density % sol: 51.62 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / Details: 20%(w/v) PEG2250, 0.2M Calcium chloride dihydrate |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 1 Å |
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Nov 23, 2020 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.94→132.42 Å / Num. obs: 39265 / % possible obs: 98.87 % / Redundancy: 5.1 % / CC1/2: 1 / Rmerge(I) obs: 0.069 / Net I/σ(I): 12.98 |
Reflection shell | Resolution: 2.94→3.08 Å / Rmerge(I) obs: 0.746 / Num. unique obs: 3895 / CC1/2: 0.842 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3W3G Resolution: 2.943→132.42 Å / Cor.coef. Fo:Fc: 0.906 / Cor.coef. Fo:Fc free: 0.915 / Cross valid method: THROUGHOUT / SU Rfree Blow DPI: 0.433
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Displacement parameters | Biso mean: 91.02 Å2
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Refine analyze | Luzzati coordinate error obs: 0.47 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.943→132.42 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.943→3.08 Å
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Refinement TLS params. | Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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