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Yorodumi- PDB-8gmd: CRYSTAL STRUCTURE OF AP2 ASSOCIATED KINASE 1 COMPLEXED WITH (5P)-... -
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-Basic information
Entry | Database: PDB / ID: 8gmd | ||||||
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Title | CRYSTAL STRUCTURE OF AP2 ASSOCIATED KINASE 1 COMPLEXED WITH (5P)-3-({(8R)-5-[(4-aminopiperidin-1-yl)methyl]pyrrolo[2,1-f][1,2,4]triazin-4-yl}amino)-5-[2-(propan-2-yl)-2H-tetrazol-5-yl]phenol | ||||||
Components | AP2-associated protein kinase 1 | ||||||
Keywords | TRANSFERASE / AP2 ASSOCIATED KINASE 1 / AAK1 / kinase / ligand inhibitor | ||||||
Function / homology | Function and homology information presynaptic endocytosis / regulation of clathrin-dependent endocytosis / AP-2 adaptor complex binding / membrane organization / Notch binding / clathrin-coated vesicle / positive regulation of Notch signaling pathway / cell leading edge / clathrin-coated pit / terminal bouton ...presynaptic endocytosis / regulation of clathrin-dependent endocytosis / AP-2 adaptor complex binding / membrane organization / Notch binding / clathrin-coated vesicle / positive regulation of Notch signaling pathway / cell leading edge / clathrin-coated pit / terminal bouton / Cargo recognition for clathrin-mediated endocytosis / Clathrin-mediated endocytosis / presynapse / regulation of protein localization / protein stabilization / non-specific serine/threonine protein kinase / protein phosphorylation / intracellular membrane-bounded organelle / protein serine kinase activity / protein serine/threonine kinase activity / ATP binding / plasma membrane / cytosol Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.2 Å | ||||||
Authors | Muckelbauer, J.K. | ||||||
Funding support | 1items
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Citation | Journal: Med.Chem.Res. / Year: 2023 Title: Discovery of pyrrolo[2,1- f ][1,2,4]triazine-based inhibitors of adaptor protein 2-associated kinase 1 for the treatment of pain. Authors: Dzierba, C.D. / Dasgupta, B. / Karageorge, G. / Kostich, W. / Hamman, B. / Allen, J. / Esposito, K.M. / Padmanabha, R. / Grace, J. / Lentz, K. / Morrison, J. / Morgan, D. / Easton, A. / ...Authors: Dzierba, C.D. / Dasgupta, B. / Karageorge, G. / Kostich, W. / Hamman, B. / Allen, J. / Esposito, K.M. / Padmanabha, R. / Grace, J. / Lentz, K. / Morrison, J. / Morgan, D. / Easton, A. / Bourin, C. / Browning, M.R. / Rajamani, R. / Good, A. / Parker, D.D. / Muckelbauer, J.K. / Khan, J. / Camac, D. / Ghosh, K. / Halan, V. / Lippy, J.S. / Santone, K.S. / Denton, R.R. / Westphal, R. / Bristow, L.J. / Conway, C.M. / Bronson, J.J. / Macor, J.E. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8gmd.cif.gz | 131.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8gmd.ent.gz | 98.8 KB | Display | PDB format |
PDBx/mmJSON format | 8gmd.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8gmd_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 8gmd_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 8gmd_validation.xml.gz | 22.7 KB | Display | |
Data in CIF | 8gmd_validation.cif.gz | 31.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/gm/8gmd ftp://data.pdbj.org/pub/pdb/validation_reports/gm/8gmd | HTTPS FTP |
-Related structure data
Related structure data | 8gmcSC 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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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 36095.391 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: AAK1, KIAA1048 / Production host: Escherichia coli BL21(DE3) (bacteria) References: UniProt: Q2M2I8, non-specific serine/threonine protein kinase #2: Chemical | #3: Chemical | ChemComp-SO4 / #4: 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: 3.08 Å3/Da / Density % sol: 60.04 % |
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Crystal grow | Temperature: 296 K / Method: vapor diffusion, hanging drop / pH: 6 Details: 1.2M AmSO4, 0.1M tri-Na Citrate pH 6.0, 3% isopropanol, 296K |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I02 / Wavelength: 0.98 Å |
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: May 16, 2009 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.98 Å / Relative weight: 1 |
Reflection | Resolution: 2.2→50 Å / Num. obs: 46886 / % possible obs: 99.3 % / Redundancy: 8.8 % / Rmerge(I) obs: 0.086 / Net I/σ(I): 22.1 |
Reflection shell | Resolution: 2.2→2.28 Å / Redundancy: 4.3 % / Rmerge(I) obs: 0.522 / Mean I/σ(I) obs: 2.9 / Num. unique obs: 4599 / % possible all: 99.5 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 8GMC Resolution: 2.2→32.21 Å / Cor.coef. Fo:Fc: 0.925 / Cor.coef. Fo:Fc free: 0.916 / Cross valid method: THROUGHOUT / σ(F): 0 / SU Rfree Blow DPI: 0.168
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Displacement parameters | Biso mean: 50.12 Å2
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Refine analyze | Luzzati coordinate error obs: 0.354 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.2→32.21 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.2→2.26 Å / Total num. of bins used: 20
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