+Open data
-Basic information
Entry | Database: PDB / ID: 5ho8 | ||||||
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Title | DISCOVERY OF NOVEL 7-AZAINDOLES AS PDK1 INHIBITORS | ||||||
Components | 3-phosphoinositide-dependent protein kinase 1 | ||||||
Keywords | TRANSFERASE / PDK1 inhibitor | ||||||
Function / homology | Function and homology information 3-phosphoinositide-dependent protein kinase activity / Activation of AKT2 / regulation of mast cell degranulation / negative regulation of toll-like receptor signaling pathway / type B pancreatic cell development / positive regulation of phospholipase activity / RSK activation / hyperosmotic response / regulation of canonical NF-kappaB signal transduction / positive regulation of vascular endothelial cell proliferation ...3-phosphoinositide-dependent protein kinase activity / Activation of AKT2 / regulation of mast cell degranulation / negative regulation of toll-like receptor signaling pathway / type B pancreatic cell development / positive regulation of phospholipase activity / RSK activation / hyperosmotic response / regulation of canonical NF-kappaB signal transduction / positive regulation of vascular endothelial cell proliferation / negative regulation of cardiac muscle cell apoptotic process / phospholipase activator activity / positive regulation of sprouting angiogenesis / Constitutive Signaling by AKT1 E17K in Cancer / CD28 dependent PI3K/Akt signaling / phospholipase binding / positive regulation of blood vessel endothelial cell migration / Role of LAT2/NTAL/LAB on calcium mobilization / Estrogen-stimulated signaling through PRKCZ / SARS-CoV-2 targets host intracellular signalling and regulatory pathways / negative regulation of endothelial cell apoptotic process / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / extrinsic apoptotic signaling pathway / RHO GTPases activate PKNs / cellular response to epidermal growth factor stimulus / GPVI-mediated activation cascade / T cell costimulation / activation of protein kinase B activity / Integrin signaling / insulin-like growth factor receptor signaling pathway / positive regulation of release of sequestered calcium ion into cytosol / VEGFR2 mediated vascular permeability / VEGFR2 mediated cell proliferation / cell projection / calcium-mediated signaling / positive regulation of protein localization to plasma membrane / peptidyl-threonine phosphorylation / negative regulation of transforming growth factor beta receptor signaling pathway / negative regulation of protein kinase activity / epidermal growth factor receptor signaling pathway / CLEC7A (Dectin-1) signaling / FCERI mediated NF-kB activation / G beta:gamma signalling through PI3Kgamma / cellular response to insulin stimulus / positive regulation of angiogenesis / Regulation of TP53 Degradation / cell migration / Downstream TCR signaling / insulin receptor signaling pathway / PIP3 activates AKT signaling / cytoplasmic vesicle / actin cytoskeleton organization / protein autophosphorylation / postsynaptic density / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / non-specific serine/threonine protein kinase / intracellular signal transduction / protein phosphorylation / protein serine kinase activity / focal adhesion / protein serine/threonine kinase activity / ATP binding / nucleus / plasma membrane / cytoplasm / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.7 Å | ||||||
Authors | Wucherer-Plietker, M. / Esdar, C. / Knoechel, T. / Hillertz, P. / Heinrich, T. / Buchstaller, H.P. / Greiner, H. / Dorsch, D. / Calderini, M. / Bruge, D. ...Wucherer-Plietker, M. / Esdar, C. / Knoechel, T. / Hillertz, P. / Heinrich, T. / Buchstaller, H.P. / Greiner, H. / Dorsch, D. / Calderini, M. / Bruge, D. / Mueller, T.J.J. / Graedler, U. | ||||||
Citation | Journal: Bioorg.Med.Chem.Lett. / Year: 2016 Title: Discovery of novel 7-azaindoles as PDK1 inhibitors. Authors: Wucherer-Plietker, M. / Merkul, E. / Muller, T.J. / Esdar, C. / Knochel, T. / Heinrich, T. / Buchstaller, H.P. / Greiner, H. / Dorsch, D. / Finsinger, D. / Calderini, M. / Bruge, D. / Gradler, U. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5ho8.cif.gz | 130.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5ho8.ent.gz | 101.1 KB | Display | PDB format |
PDBx/mmJSON format | 5ho8.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5ho8_validation.pdf.gz | 688.1 KB | Display | wwPDB validaton report |
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Full document | 5ho8_full_validation.pdf.gz | 690.8 KB | Display | |
Data in XML | 5ho8_validation.xml.gz | 13.1 KB | Display | |
Data in CIF | 5ho8_validation.cif.gz | 17.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ho/5ho8 ftp://data.pdbj.org/pub/pdb/validation_reports/ho/5ho8 | HTTPS FTP |
-Related structure data
Related structure data | 5hkmC 5hngC 5ho7C 1okzS 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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Unit cell |
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-Components
#1: Protein | Mass: 35427.609 Da / Num. of mol.: 1 / Fragment: KINASE DOMAIN, RESIDUES 51-359 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PDPK1, PDK1 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: O15530, non-specific serine/threonine protein kinase | ||
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#2: Chemical | ChemComp-63E / | ||
#3: Chemical | ChemComp-SO4 / #4: Water | ChemComp-HOH / | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.91 Å3/Da / Density % sol: 57.71 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 8.6 / Details: 100 mM Tris-HCl, 1.8 M NH4-sulfate / PH range: 8.6 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X06DA / Wavelength: 1 Å |
Detector | Type: MARMOSAIC 225 mm CCD / Detector: CCD / Date: Oct 12, 2006 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.7→50 Å / Num. obs: 10281 / % possible obs: 89.2 % / Redundancy: 3.2 % / Biso Wilson estimate: 66.63 Å2 / Rmerge(I) obs: 0.064 / Net I/σ(I): 11.5 |
Reflection shell | Resolution: 2.7→2.8 Å / % possible all: 36.5 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1OKZ Resolution: 2.7→37.44 Å / Cor.coef. Fo:Fc: 0.943 / Cor.coef. Fo:Fc free: 0.898 / Rfactor Rfree error: 0 / SU R Cruickshank DPI: 0.901 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.876 / SU Rfree Blow DPI: 0.303 / SU Rfree Cruickshank DPI: 0.308
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Displacement parameters | Biso mean: 55.18 Å2
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Refine analyze | Luzzati coordinate error obs: 0.31 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.7→37.44 Å
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Refine LS restraints |
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LS refinement shell | Highest resolution: 2.7 Å / Rfactor Rfree error: 0
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Refinement TLS params. | Method: refined / Origin x: 41.8768 Å / Origin y: 18.8884 Å / Origin z: 13.608 Å
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Refinement TLS group | Selection details: { A|* } |