+Open data
-Basic information
Entry | Database: PDB / ID: 8out | ||||||
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Title | CRYSTAL STRUCTURE OF DLK IN COMPLEX WITH COMPOUND 22 | ||||||
Components | Mitogen-activated protein kinase kinase kinase 12 | ||||||
Keywords | SIGNALING PROTEIN / DLK / KINASE / INHIBITOR / TRANSFERASE-INHIBITOR / M3K12 | ||||||
Function / homology | Function and homology information mitogen-activated protein kinase kinase kinase / JUN kinase kinase kinase activity / negative regulation of motor neuron apoptotic process / positive regulation of protein kinase activity / positive regulation of JUN kinase activity / JNK cascade / protein serine/threonine kinase activator activity / post-translational protein modification / growth cone / peptidyl-serine phosphorylation ...mitogen-activated protein kinase kinase kinase / JUN kinase kinase kinase activity / negative regulation of motor neuron apoptotic process / positive regulation of protein kinase activity / positive regulation of JUN kinase activity / JNK cascade / protein serine/threonine kinase activator activity / post-translational protein modification / growth cone / peptidyl-serine phosphorylation / protein autophosphorylation / positive regulation of ERK1 and ERK2 cascade / protein kinase activity / intracellular signal transduction / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / protein kinase binding / positive regulation of DNA-templated transcription / protein homodimerization activity / ATP binding / membrane / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.935 Å | ||||||
Authors | Zebisch, M. / Akkermans, O. / Barker, J.J. / Cross, J.B. | ||||||
Funding support | United States, 1items
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Citation | Journal: J.Med.Chem. / Year: 2023 Title: Discovery of IACS-52825, a Potent and Selective DLK Inhibitor for Treatment of Chemotherapy-Induced Peripheral Neuropathy. Authors: Le, K. / Soth, M.J. / Cross, J.B. / Liu, G. / Ray, W.J. / Ma, J. / Goodwani, S.G. / Acton, P.J. / Buggia-Prevot, V. / Akkermans, O. / Barker, J. / Conner, M.L. / Jiang, Y. / Liu, Z. / ...Authors: Le, K. / Soth, M.J. / Cross, J.B. / Liu, G. / Ray, W.J. / Ma, J. / Goodwani, S.G. / Acton, P.J. / Buggia-Prevot, V. / Akkermans, O. / Barker, J. / Conner, M.L. / Jiang, Y. / Liu, Z. / McEwan, P. / Warner-Schmidt, J. / Xu, A. / Zebisch, M. / Heijnen, C.J. / Abrahams, B. / Jones, P. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8out.cif.gz | 121.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8out.ent.gz | 95.1 KB | Display | PDB format |
PDBx/mmJSON format | 8out.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ou/8out ftp://data.pdbj.org/pub/pdb/validation_reports/ou/8out | HTTPS FTP |
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-Related structure data
Related structure data | 8ourC 8ousC 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
#1: Protein | Mass: 34018.031 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MAP3K12, ZPK / Production host: Trichoplusia ni (cabbage looper) References: UniProt: Q12852, mitogen-activated protein kinase kinase kinase |
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#2: Chemical | ChemComp-W3C / ( |
#3: Water | ChemComp-HOH / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 1.94 Å3/Da / Density % sol: 36.46 % / Description: thin plates |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, hanging drop / pH: 7.7 Details: 20% PEG 3350, 0.2 M magnesium acetate, 0.1 M HEPES/NaOH pH 7.5-7.9 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 0.9999 Å |
Detector | Type: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Jun 7, 2020 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9999 Å / Relative weight: 1 |
Reflection | Resolution: 1.935→59.37 Å / Num. obs: 13835 / % possible obs: 70.1 % / Redundancy: 3.4 % / CC1/2: 0.995 / Rmerge(I) obs: 0.1 / Rpim(I) all: 0.064 / Rrim(I) all: 0.119 / Net I/σ(I): 5.4 |
Reflection shell | Resolution: 1.935→2.106 Å / Redundancy: 3.3 % / Rmerge(I) obs: 0.838 / Mean I/σ(I) obs: 1.3 / Num. unique obs: 692 / CC1/2: 0.561 / Rpim(I) all: 0.544 / Rrim(I) all: 1.003 / % possible all: 15.8 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.935→59.37 Å / Cor.coef. Fo:Fc: 0.945 / Cor.coef. Fo:Fc free: 0.926 / SU R Cruickshank DPI: 0.29 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.286 / SU Rfree Blow DPI: 0.198 / SU Rfree Cruickshank DPI: 0.201
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Displacement parameters | Biso mean: 35.44 Å2
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Refine analyze | Luzzati coordinate error obs: 0.3 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.935→59.37 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.94→2.07 Å / Total num. of bins used: 33
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Refinement TLS params. | Method: refined / Origin x: 3.2569 Å / Origin y: 2.5382 Å / Origin z: 22.9871 Å
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Refinement TLS group | Selection details: { A|* } |