+Open data
-Basic information
Entry | Database: PDB / ID: 6x82 | ||||||
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Title | Crystal Structure of TNFalpha with isoquinoline compound 4 | ||||||
Components | Tumor necrosis factor | ||||||
Keywords | CYTOKINE / Trimer / inhibitor complex | ||||||
Function / homology | Function and homology information negative regulation of L-glutamate import across plasma membrane / negative regulation of bile acid secretion / response to Gram-negative bacterium / positive regulation of neutrophil activation / negative regulation of branching involved in lung morphogenesis / positive regulation of interleukin-33 production / positive regulation of blood microparticle formation / positive regulation of chronic inflammatory response to antigenic stimulus / positive regulation of fractalkine production / positive regulation of vitamin D biosynthetic process ...negative regulation of L-glutamate import across plasma membrane / negative regulation of bile acid secretion / response to Gram-negative bacterium / positive regulation of neutrophil activation / negative regulation of branching involved in lung morphogenesis / positive regulation of interleukin-33 production / positive regulation of blood microparticle formation / positive regulation of chronic inflammatory response to antigenic stimulus / positive regulation of fractalkine production / positive regulation of vitamin D biosynthetic process / response to macrophage colony-stimulating factor / positive regulation of leukocyte adhesion to arterial endothelial cell / positive regulation of translational initiation by iron / response to 3,3',5-triiodo-L-thyronine / regulation of membrane lipid metabolic process / regulation of endothelial cell apoptotic process / regulation of branching involved in salivary gland morphogenesis / chronic inflammatory response to antigenic stimulus / negative regulation of protein-containing complex disassembly / response to gold nanoparticle / positive regulation of humoral immune response mediated by circulating immunoglobulin / : / positive regulation of hair follicle development / negative regulation of myelination / death receptor agonist activity / negative regulation of vascular wound healing / negative regulation of bicellular tight junction assembly / negative regulation of amyloid-beta clearance / negative regulation of cytokine production involved in immune response / response to isolation stress / inflammatory response to wounding / cellular response to toxic substance / positive regulation of calcidiol 1-monooxygenase activity / positive regulation of I-kappaB phosphorylation / sequestering of triglyceride / positive regulation of interleukin-18 production / positive regulation of action potential / TNF signaling / positive regulation of protein transport / epithelial cell proliferation involved in salivary gland morphogenesis / toll-like receptor 3 signaling pathway / embryonic digestive tract development / leukocyte migration involved in inflammatory response / necroptotic signaling pathway / vascular endothelial growth factor production / positive regulation of calcineurin-NFAT signaling cascade / positive regulation of neuroinflammatory response / positive regulation of mononuclear cell migration / leukocyte tethering or rolling / response to fructose / positive regulation of synoviocyte proliferation / positive regulation of fever generation / negative regulation of myoblast differentiation / regulation of establishment of endothelial barrier / negative regulation of glucose import / endothelial cell apoptotic process / macrophage activation involved in immune response / positive regulation of protein localization to cell surface / negative regulation of oxidative phosphorylation / TNFR1-mediated ceramide production / positive regulation of cytokine production involved in inflammatory response / positive regulation of osteoclast differentiation / regulation of metabolic process / tumor necrosis factor receptor binding / negative regulation of systemic arterial blood pressure / positive regulation of extrinsic apoptotic signaling pathway / positive regulation of chemokine (C-X-C motif) ligand 2 production / positive regulation of programmed cell death / regulation of immunoglobulin production / positive regulation of hepatocyte proliferation / positive regulation of protein-containing complex disassembly / positive regulation of heterotypic cell-cell adhesion / positive regulation of podosome assembly / positive regulation of membrane protein ectodomain proteolysis / negative regulation of blood vessel endothelial cell migration / negative regulation of lipid storage / regulation of canonical NF-kappaB signal transduction / negative regulation of mitotic cell cycle / regulation of reactive oxygen species metabolic process / regulation of fat cell differentiation / TNFR1-induced proapoptotic signaling / positive regulation of leukocyte adhesion to vascular endothelial cell / cortical actin cytoskeleton organization / response to L-glutamate / negative regulation of heart rate / positive regulation of amyloid-beta formation / positive regulation of DNA biosynthetic process / negative regulation of viral genome replication / negative regulation of osteoblast differentiation / regulation of synapse organization / negative regulation of fat cell differentiation / positive regulation of cysteine-type endopeptidase activity involved in apoptotic process / negative regulation of endothelial cell proliferation / Interleukin-10 signaling / negative regulation of interleukin-6 production / regulation of insulin secretion / positive regulation of glial cell proliferation / phagocytic cup / humoral immune response / negative regulation of signaling receptor activity Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.75 Å | ||||||
Authors | Longenecker, K.L. / Stoll, V.S. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2021 Title: Development of Orally Efficacious Allosteric Inhibitors of TNF alpha via Fragment-Based Drug Design. Authors: Dietrich, J.D. / Longenecker, K.L. / Wilson, N.S. / Goess, C. / Panchal, S.C. / Swann, S.L. / Petros, A.M. / Hobson, A.D. / Ihle, D. / Song, D. / Richardson, P. / Comess, K.M. / Cox, P.B. / ...Authors: Dietrich, J.D. / Longenecker, K.L. / Wilson, N.S. / Goess, C. / Panchal, S.C. / Swann, S.L. / Petros, A.M. / Hobson, A.D. / Ihle, D. / Song, D. / Richardson, P. / Comess, K.M. / Cox, P.B. / Dombrowski, A. / Sarris, K. / Donnelly-Roberts, D.L. / Duignan, D.B. / Gomtsyan, A. / Jung, P. / Krueger, A.C. / Mathieu, S. / McClure, A. / Stoll, V.S. / Wetter, J. / Mankovich, J.A. / Hajduk, P.J. / Vasudevan, A. / Stoffel, R.H. / Sun, C. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6x82.cif.gz | 184.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6x82.ent.gz | 144.9 KB | Display | PDB format |
PDBx/mmJSON format | 6x82.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6x82_validation.pdf.gz | 972.2 KB | Display | wwPDB validaton report |
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Full document | 6x82_full_validation.pdf.gz | 980.2 KB | Display | |
Data in XML | 6x82_validation.xml.gz | 33.5 KB | Display | |
Data in CIF | 6x82_validation.cif.gz | 46.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/x8/6x82 ftp://data.pdbj.org/pub/pdb/validation_reports/x8/6x82 | HTTPS FTP |
-Related structure data
Related structure data | 6x81C 6x83C 6x85C 6x86C 1tnfS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 17501.854 Da / Num. of mol.: 6 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TNF, TNFA, TNFSF2 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P01375 #2: Chemical | #3: Water | ChemComp-HOH / | 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: 2.78 Å3/Da / Density % sol: 55.75 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion / pH: 6.5 Details: 15% PEG8000, 0.2M Magnesium acetate, 0.05M sodium cacodylate, pH 6.5 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Feb 8, 2012 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.75→82 Å / Num. obs: 31085 / % possible obs: 99.7 % / Redundancy: 6.3 % / Biso Wilson estimate: 78.02 Å2 / Rmerge(I) obs: 0.104 / Net I/σ(I): 14 |
Reflection shell | Resolution: 2.75→2.8 Å / Rmerge(I) obs: 0.95 / Num. unique obs: 1540 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1tnf Resolution: 2.75→69.45 Å / Cor.coef. Fo:Fc: 0.933 / Cor.coef. Fo:Fc free: 0.876 / SU R Cruickshank DPI: 0.719 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.8 / SU Rfree Blow DPI: 0.297 / SU Rfree Cruickshank DPI: 0.299
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Displacement parameters | Biso max: 163.55 Å2 / Biso mean: 63.54 Å2 / Biso min: 28.08 Å2
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Refine analyze | Luzzati coordinate error obs: 0.32 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.75→69.45 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.75→2.77 Å / Rfactor Rfree error: 0 / Total num. of bins used: 50
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