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Yorodumi- PDB-6szm: Crystal structure of the ACVR1 (ALK2) kinase in complex with the ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6szm | ||||||
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Title | Crystal structure of the ACVR1 (ALK2) kinase in complex with the compound M4K2009 | ||||||
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: 1.42 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: Leveraging an Open Science Drug Discovery Model to Develop CNS-Penetrant ALK2 Inhibitors for the Treatment of Diffuse Intrinsic Pontine Glioma. Authors: Smil, D. / Wong, J.F. / Williams, E.P. / Adamson, R.J. / Howarth, A. / McLeod, D.A. / Mamai, A. / Kim, S. / Wilson, B.J. / Kiyota, T. / Aman, A. / Owen, J. / Poda, G. / Horiuchi, K.Y. / ...Authors: Smil, D. / Wong, J.F. / Williams, E.P. / Adamson, R.J. / Howarth, A. / McLeod, D.A. / Mamai, A. / Kim, S. / Wilson, B.J. / Kiyota, T. / Aman, A. / Owen, J. / Poda, G. / Horiuchi, K.Y. / Kuznetsova, E. / Ma, H. / Hamblin, J.N. / Cramp, S. / Roberts, O.G. / Edwards, A.M. / Uehling, D. / Al-Awar, R. / Bullock, A.N. / O'Meara, J.A. / Isaac, M.B. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6szm.cif.gz | 445.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6szm.ent.gz | 306.7 KB | Display | PDB format |
PDBx/mmJSON format | 6szm.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6szm_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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Full document | 6szm_full_validation.pdf.gz | 1.3 MB | Display | |
Data in XML | 6szm_validation.xml.gz | 31.9 KB | Display | |
Data in CIF | 6szm_validation.cif.gz | 48.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/sz/6szm ftp://data.pdbj.org/pub/pdb/validation_reports/sz/6szm | HTTPS FTP |
-Related structure data
Related structure data | 6srhS 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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2 |
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Unit cell |
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-Components
-Protein , 1 types, 2 molecules AB
#1: Protein | Mass: 34537.633 Da / Num. of mol.: 2 / Mutation: Q207D Source method: isolated from a genetically manipulated source 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 |
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-Non-polymers , 6 types, 712 molecules
#2: Chemical | ChemComp-M2Z / #3: Chemical | ChemComp-SO4 / #4: Chemical | ChemComp-EDO / #5: Chemical | ChemComp-NH4 / | #6: Chemical | ChemComp-DMS / | #7: Water | ChemComp-HOH / | |
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-Details
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: 2.66 Å3/Da / Density % sol: 53.81 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 5.5 / Details: 2M ammonium sulfate, 0.1M bis-tris pH 5.5 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I24 / Wavelength: 0.9686 Å |
Detector | Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Jan 20, 2019 Details: Oxford Danfysik/SESO Two stage demagnification using two K-B pairs of bimorph type mirrors |
Radiation | Monochromator: ACCEL Fixed exit Double Crystal / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9686 Å / Relative weight: 1 |
Reflection | Resolution: 1.42→63.41 Å / Num. obs: 132079 / % possible obs: 100 % / Redundancy: 6.6 % / Biso Wilson estimate: 15.7 Å2 / CC1/2: 0.996 / Rmerge(I) obs: 0.105 / Rpim(I) all: 0.067 / Rrim(I) all: 0.125 / Χ2: 0.9 / Net I/σ(I): 7.2 |
Reflection shell | Resolution: 1.42→1.46 Å / Redundancy: 6.7 % / Rmerge(I) obs: 0.051 / Mean I/σ(I) obs: 19.9 / Num. unique obs: 1534 / CC1/2: 0.993 / Rpim(I) all: 0.032 / Rrim(I) all: 0.06 / Χ2: 0.53 / % possible all: 99.9 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6srh Resolution: 1.42→63.36 Å / SU ML: 0.1588 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Phase error: 20.1609
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 24.18 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.42→63.36 Å
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Refine LS restraints |
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LS refinement shell |
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