+Open data
-Basic information
Entry | Database: PDB / ID: 4aoj | ||||||
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Title | Human TrkA in complex with the inhibitor AZ-23 | ||||||
Components | HIGH AFFINITY NERVE GROWTH FACTOR RECEPTOR | ||||||
Keywords | TRANSFERASE / INHIBITOR | ||||||
Function / homology | Function and homology information behavioral response to formalin induced pain / neurotrophin p75 receptor binding / olfactory nerve development / response to hydrostatic pressure / TRKA activation by NGF / PLC-gamma1 signalling / Signalling to STAT3 / programmed cell death involved in cell development / neurotrophin receptor activity / mechanoreceptor differentiation ...behavioral response to formalin induced pain / neurotrophin p75 receptor binding / olfactory nerve development / response to hydrostatic pressure / TRKA activation by NGF / PLC-gamma1 signalling / Signalling to STAT3 / programmed cell death involved in cell development / neurotrophin receptor activity / mechanoreceptor differentiation / nerve growth factor receptor activity / neurotrophin binding / Sertoli cell development / axonogenesis involved in innervation / GPI-linked ephrin receptor activity / nerve growth factor signaling pathway / Retrograde neurotrophin signalling / nerve growth factor binding / NGF-independant TRKA activation / sympathetic nervous system development / Signalling to p38 via RIT and RIN / ARMS-mediated activation / positive regulation of Ras protein signal transduction / positive regulation of programmed cell death / positive regulation of synapse assembly / PI3K/AKT activation / Frs2-mediated activation / peptidyl-tyrosine autophosphorylation / detection of temperature stimulus involved in sensory perception of pain / neurotrophin TRK receptor signaling pathway / response to axon injury / Signalling to RAS / neuron development / transmembrane receptor protein tyrosine kinase activity / positive regulation of synaptic transmission, glutamatergic / detection of mechanical stimulus involved in sensory perception of pain / response to electrical stimulus / response to nutrient levels / B cell differentiation / cellular response to nerve growth factor stimulus / positive regulation of GTPase activity / axon guidance / receptor protein-tyrosine kinase / kinase binding / circadian rhythm / peptidyl-tyrosine phosphorylation / positive regulation of neuron projection development / cellular response to nicotine / recycling endosome membrane / positive regulation of angiogenesis / neuron projection development / late endosome / early endosome membrane / late endosome membrane / positive regulation of NF-kappaB transcription factor activity / protein tyrosine kinase activity / neuron apoptotic process / protein autophosphorylation / negative regulation of neuron apoptotic process / receptor complex / positive regulation of ERK1 and ERK2 cascade / learning or memory / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / endosome membrane / early endosome / positive regulation of protein phosphorylation / response to xenobiotic stimulus / protein phosphorylation / negative regulation of cell population proliferation / axon / neuronal cell body / dendrite / negative regulation of apoptotic process / cell surface / protein homodimerization activity / protein-containing complex / ATP binding / identical protein binding / plasma membrane Similarity search - Function | ||||||
Biological species | HOMO SAPIENS (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.75 Å | ||||||
Authors | Wang, T. / Lamb, M.L. / Block, M.H. / Davies, A.M. / Han, Y. / Hoffmann, E. / Ioannidis, S. / Josey, J.A. / Liu, Z. / Lyne, P.D. ...Wang, T. / Lamb, M.L. / Block, M.H. / Davies, A.M. / Han, Y. / Hoffmann, E. / Ioannidis, S. / Josey, J.A. / Liu, Z. / Lyne, P.D. / MacIntyre, T. / Mohr, P.J. / Omer, C.A. / Sjogren, T. / Thress, K. / Wang, B. / Wang, H. / Yu, D. / Zhang, H. | ||||||
Citation | Journal: Acs Med.Chem.Lett. / Year: 2012 Title: Discovery of Disubstituted Imidazo[4,5-B]Pyridines and Purines as Potent Trka Inhibitors Authors: Wang, T. / Lamb, M.L. / Block, M.H. / Davies, A.M. / Han, Y. / Hoffmann, E. / Ioannidis, S. / Josey, J.A. / Liu, Z. / Lyne, P.D. / Macintyre, T. / Mohr, P.J. / Omer, C.A. / Sjogren, T. / ...Authors: Wang, T. / Lamb, M.L. / Block, M.H. / Davies, A.M. / Han, Y. / Hoffmann, E. / Ioannidis, S. / Josey, J.A. / Liu, Z. / Lyne, P.D. / Macintyre, T. / Mohr, P.J. / Omer, C.A. / Sjogren, T. / Thress, K. / Wang, B. / Wang, H. / Yu, D. / Zhang, H. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 4aoj.cif.gz | 172.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb4aoj.ent.gz | 136 KB | Display | PDB format |
PDBx/mmJSON format | 4aoj.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 4aoj_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 4aoj_full_validation.pdf.gz | 1.5 MB | Display | |
Data in XML | 4aoj_validation.xml.gz | 30.6 KB | Display | |
Data in CIF | 4aoj_validation.cif.gz | 41.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ao/4aoj ftp://data.pdbj.org/pub/pdb/validation_reports/ao/4aoj | HTTPS FTP |
-Related structure data
Related structure data | 1r0pS S: Starting model for refinement |
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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: 36898.379 Da / Num. of mol.: 3 / Fragment: KINASE DOMAIN, RESIDUES 473-796 Source method: isolated from a genetically manipulated source Source: (gene. exp.) HOMO SAPIENS (human) / Plasmid: PFASTBAC HTB / Cell line (production host): SF9 / Production host: SPODOPTERA FRUGIPERDA (fall armyworm) References: UniProt: P04629, receptor protein-tyrosine kinase #2: Chemical | #3: Chemical | ChemComp-ZN / #4: Water | ChemComp-HOH / | |
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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: 3.56 Å3/Da / Density % sol: 65 % / Description: NONE |
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Crystal grow | Method: vapor diffusion, hanging drop / pH: 8 Details: HANGING DROP METHOD. 1 UL TRKA AT 10 MG/ML IN 10 MG/ML IN 20 MM TRIS PH 8.5, 0.1% CHAPS, 1MM TCEP, 8.7% GLYCEROL MIXED WITH 1 UL MOTHER LIQUOR CONTAINING 35% W/V GLYCEROL, 140 MM NA/K ...Details: HANGING DROP METHOD. 1 UL TRKA AT 10 MG/ML IN 10 MG/ML IN 20 MM TRIS PH 8.5, 0.1% CHAPS, 1MM TCEP, 8.7% GLYCEROL MIXED WITH 1 UL MOTHER LIQUOR CONTAINING 35% W/V GLYCEROL, 140 MM NA/K TARTRATE, 100 MM HEPES PH 8.0 SUPPLEMENTED WITH 40 MM ZINC CHLORIDE. |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: ESRF / Beamline: ID14-4 / Wavelength: 0.94 |
Detector | Type: ADSC CCD / Detector: CCD / Date: Nov 2, 2005 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.94 Å / Relative weight: 1 |
Reflection | Resolution: 2.75→42.06 Å / Num. obs: 41385 / % possible obs: 99.9 % / Observed criterion σ(I): 2 / Redundancy: 3.6 % / Rmerge(I) obs: 0.07 / Net I/σ(I): 13 |
Reflection shell | Resolution: 2.75→2.82 Å / Redundancy: 3.6 % / Rmerge(I) obs: 0.38 / Mean I/σ(I) obs: 3 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 1R0P Resolution: 2.75→40 Å / Cor.coef. Fo:Fc: 0.921 / Cor.coef. Fo:Fc free: 0.907 / SU B: 8.435 / SU ML: 0.175 / Cross valid method: THROUGHOUT / ESU R: 0.455 / ESU R Free: 0.284 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS.
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 55.732 Å2
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Refinement step | Cycle: LAST / Resolution: 2.75→40 Å
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Refine LS restraints |
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