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Yorodumi- PDB-8c7w: Crystal structure of the ACVR1 (ALK2) kinase in complex with the ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8c7w | ||||||
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Title | Crystal structure of the ACVR1 (ALK2) kinase in complex with the compound M4K2304 | ||||||
Components | Activin receptor type I | ||||||
Keywords | SIGNALING PROTEIN / BMP signalling Kinase Inhibitor | ||||||
Function / homology | Function and homology information endocardial cushion cell fate commitment / mitral valve morphogenesis / endocardial cushion fusion / BMP receptor complex / BMP receptor activity / atrial septum primum morphogenesis / 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 / BMP receptor activity / atrial septum primum morphogenesis / 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 osteoblast differentiation / positive regulation of bone mineralization / 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 / 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: 2.26 Å | ||||||
Authors | Cros, J. / Williams, E.P. / Sweeney, M.N. / Smil, D. / Gonzalez-Alvarez, H. / Al-awar, R. / Bullock, A.N. | ||||||
Funding support | Switzerland, 1items
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Citation | Journal: J.Med.Chem. / Year: 2024 Title: Discovery of Conformationally Constrained ALK2 Inhibitors. Authors: Gonzalez-Alvarez, H. / Ensan, D. / Xin, T. / Wong, J.F. / Zepeda-Velazquez, C.A. / Cros, J. / Sweeney, M.N. / Hoffer, L. / Kiyota, T. / Wilson, B.J. / Aman, A. / Roberts, O. / Isaac, M.B. / ...Authors: Gonzalez-Alvarez, H. / Ensan, D. / Xin, T. / Wong, J.F. / Zepeda-Velazquez, C.A. / Cros, J. / Sweeney, M.N. / Hoffer, L. / Kiyota, T. / Wilson, B.J. / Aman, A. / Roberts, O. / Isaac, M.B. / Bullock, A.N. / Smil, D. / 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 | 8c7w.cif.gz | 95.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8c7w.ent.gz | 57.2 KB | Display | PDB format |
PDBx/mmJSON format | 8c7w.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/c7/8c7w ftp://data.pdbj.org/pub/pdb/validation_reports/c7/8c7w | HTTPS FTP |
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-Related structure data
Related structure data | 8c7zC 3mtfS 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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Unit cell |
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-Components
#1: Protein | Mass: 34537.633 Da / Num. of mol.: 1 / Mutation: Q207D Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ACVR1 / Plasmid: pFB-LIC-Bse / Cell line (production host): Sf9 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: Q04771, receptor protein serine/threonine kinase | ||||||
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#2: Chemical | ChemComp-U0C / | ||||||
#3: Chemical | ChemComp-SO4 / #4: Chemical | ChemComp-EDO / #5: 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: 2.66 Å3/Da / Density % sol: 53.86 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 8.5 Details: 1.6M ammonium sulfate, 0.1M tris pH 8.5, 4% glycerol |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.976254 Å |
Detector | Type: DECTRIS EIGER2 XE 16M / Detector: PIXEL / Date: Sep 17, 2022 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.976254 Å / Relative weight: 1 |
Reflection | Resolution: 2.26→57.2 Å / Num. obs: 17992 / % possible obs: 100 % / Redundancy: 20.03 % / Biso Wilson estimate: 33.11 Å2 / CC1/2: 0.9883 / Rmerge(I) obs: 0.4368 / Net I/σ(I): 3.6 |
Reflection shell | Resolution: 2.26→2.3 Å / Redundancy: 20.62 % / Rmerge(I) obs: 2.1056 / Mean I/σ(I) obs: 0.54 / Num. unique obs: 874 / CC1/2: 0.8165 / % possible all: 98.76 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3MTF Resolution: 2.26→57.2 Å / SU ML: 0.3373 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 25.7702 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 32.59 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.26→57.2 Å
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Refine LS restraints |
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LS refinement shell |
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