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Yorodumi- PDB-6t6d: Crystal structure of the ACVR1 (ALK2) kinase in complex with the ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6t6d | ||||||
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Title | Crystal structure of the ACVR1 (ALK2) kinase in complex with the compound M4K2149 | ||||||
Components | Activin receptor type I | ||||||
Keywords | SIGNALING PROTEIN / KINASE / BMP / INHIBITOR / SIGNALLING | ||||||
Function / homology | Function and homology information endocardial cushion cell fate commitment / mitral valve morphogenesis / endocardial cushion fusion / BMP receptor complex / atrial septum primum morphogenesis / BMP receptor activity / cardiac muscle cell fate commitment / acute inflammatory response / activin receptor activity, type I / positive regulation of cardiac epithelial to mesenchymal transition ...endocardial cushion cell fate commitment / mitral valve morphogenesis / endocardial cushion fusion / BMP receptor complex / atrial septum primum morphogenesis / BMP receptor activity / cardiac muscle cell fate commitment / acute inflammatory response / activin receptor activity, type I / positive regulation of cardiac epithelial to mesenchymal transition / positive regulation of determination of dorsal identity / transforming growth factor beta receptor activity, type I / activin receptor complex / endocardial cushion formation / smooth muscle cell differentiation / receptor protein serine/threonine kinase / transmembrane receptor protein serine/threonine kinase activity / pharyngeal system development / activin binding / cellular response to BMP stimulus / activin receptor signaling pathway / negative regulation of activin receptor signaling pathway / transforming growth factor beta binding / embryonic heart tube morphogenesis / gastrulation with mouth forming second / dorsal/ventral pattern formation / determination of left/right symmetry / neural crest cell migration / atrioventricular valve morphogenesis / branching involved in blood vessel morphogenesis / negative regulation of G1/S transition of mitotic cell cycle / ventricular septum morphogenesis / SMAD binding / germ cell development / peptide hormone binding / positive regulation of SMAD protein signal transduction / mesoderm formation / regulation of ossification / BMP signaling pathway / positive regulation of bone mineralization / positive regulation of osteoblast differentiation / negative regulation of signal transduction / transforming growth factor beta receptor signaling pathway / protein tyrosine kinase binding / negative regulation of extrinsic apoptotic signaling pathway / cellular response to growth factor stimulus / positive regulation of peptidyl-tyrosine phosphorylation / apical part of cell / heart development / in utero embryonic development / protein kinase activity / positive regulation of cell migration / cadherin binding / phosphorylation / protein serine/threonine kinase activity / positive regulation of DNA-templated transcription / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / ATP binding / metal ion binding / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.56 Å | ||||||
Authors | Adamson, R.J. / Williams, E.P. / Smil, D. / Burgess-Brown, N. / von Delft, F. / Arrowsmith, C.H. / Edwards, A.M. / Bountra, C. / Bullock, A.N. | ||||||
Citation | Journal: J.Med.Chem. / Year: 2020 Title: Targeting ALK2: An Open Science Approach to Developing Therapeutics for the Treatment of Diffuse Intrinsic Pontine Glioma. Authors: Ensan, D. / Smil, D. / Zepeda-Velazquez, C.A. / Panagopoulos, D. / Wong, J.F. / Williams, E.P. / Adamson, R. / Bullock, A.N. / Kiyota, T. / Aman, A. / Roberts, O.G. / Edwards, A.M. / ...Authors: Ensan, D. / Smil, D. / Zepeda-Velazquez, C.A. / Panagopoulos, D. / Wong, J.F. / Williams, E.P. / Adamson, R. / Bullock, A.N. / Kiyota, T. / Aman, A. / Roberts, O.G. / Edwards, A.M. / O'Meara, J.A. / Isaac, M.B. / Al-Awar, R. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6t6d.cif.gz | 294.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6t6d.ent.gz | 192.7 KB | Display | PDB format |
PDBx/mmJSON format | 6t6d.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6t6d_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
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Full document | 6t6d_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 6t6d_validation.xml.gz | 45.6 KB | Display | |
Data in CIF | 6t6d_validation.cif.gz | 59.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/t6/6t6d ftp://data.pdbj.org/pub/pdb/validation_reports/t6/6t6d | HTTPS FTP |
-Related structure data
Related structure data | 8r7gC 6srhS 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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3 |
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4 |
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Unit cell |
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-Components
#1: Protein | Mass: 34537.633 Da / Num. of mol.: 4 / Mutation: Q207D Source method: isolated from a genetically manipulated source Details: Chains E, F, G and H contain ligand 149 bound to the kinase active site and SO4 as part of the crystal packing. Source: (gene. exp.) Homo sapiens (human) / Gene: ACVR1 / Cell line (production host): Sf9 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: Q04771, receptor protein serine/threonine kinase #2: Chemical | ChemComp-MM8 / #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: 2.92 Å3/Da / Density % sol: 57.9 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 4.9 Details: 0.1M citrate pH 4.9, 1M ammonium sulfate, 0.2M sodium/potassium tartrate |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.9763 Å |
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Jan 21, 2019 |
Radiation | Monochromator: double crystal / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9763 Å / Relative weight: 1 |
Reflection | Resolution: 2.56→89.13 Å / Num. obs: 50340 / % possible obs: 100 % / Redundancy: 13.3 % / Biso Wilson estimate: 58.84 Å2 / CC1/2: 0.998 / Rmerge(I) obs: 0.197 / Rpim(I) all: 0.056 / Rrim(I) all: 0.205 / Χ2: 0.99 / Net I/σ(I): 8.8 |
Reflection shell | Resolution: 2.56→2.63 Å / Redundancy: 13.5 % / Rmerge(I) obs: 3.197 / Mean I/σ(I) obs: 1.3 / Num. unique obs: 3699 / CC1/2: 0.87 / Rpim(I) all: 0.901 / Rrim(I) all: 3.323 / Χ2: 1 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6SRH Resolution: 2.56→78.45 Å / SU ML: 0.4258 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Phase error: 35.6209
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 73.66 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.56→78.45 Å
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Refine LS restraints |
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LS refinement shell |
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