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Yorodumi- PDB-6gip: Crystal structure of the ACVR1 (ALK2) kinase in complex with a Qu... -
+Open data
-Basic information
Entry | Database: PDB / ID: 6gip | ||||||
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Title | Crystal structure of the ACVR1 (ALK2) kinase in complex with a Quinazolinone based ALK2 inhibitor with a 2, 5-dimethyl core. | ||||||
Components | Activin receptor type-1 | ||||||
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 / 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: 2.17 Å | ||||||
Authors | Williams, E. / Hudson, L. / Bezerra, G.A. / Sorrell, F. / Mathea, S. / Chen, Z. / Mahajan, P. / Kupinska, K. / Hoelder, S. / Burgess-Brown, N. ...Williams, E. / Hudson, L. / Bezerra, G.A. / Sorrell, F. / Mathea, S. / Chen, Z. / Mahajan, P. / Kupinska, K. / Hoelder, S. / Burgess-Brown, N. / von Delft, F. / Arrowsmith, C.H. / Edwards, A.M. / Bountra, C. / Bullock, A.N. | ||||||
Citation | Journal: J. Med. Chem. / Year: 2018 Title: Novel Quinazolinone Inhibitors of ALK2 Flip between Alternate Binding Modes: Structure-Activity Relationship, Structural Characterization, Kinase Profiling, and Cellular Proof of Concept. Authors: Hudson, L. / Mui, J. / Vazquez, S. / Carvalho, D.M. / Williams, E. / Jones, C. / Bullock, A.N. / Hoelder, S. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6gip.cif.gz | 134.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6gip.ent.gz | 103.2 KB | Display | PDB format |
PDBx/mmJSON format | 6gip.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/gi/6gip ftp://data.pdbj.org/pub/pdb/validation_reports/gi/6gip | HTTPS FTP |
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-Related structure data
Related structure data | 6gi6C 6ginC 3h9rS 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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Unit cell |
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-Components
#1: Protein | Mass: 34537.633 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: ACVR1, ACVRLK2 / 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-EUN / | ||||
#3: Chemical | ChemComp-SO4 / #4: Chemical | #5: Water | ChemComp-HOH / | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.61 Å3/Da / Density % sol: 53.1 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 8.5 Details: 1.5M ammonium sulfate, 0.1M tris pH 8.5, 4% glycerol |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.9763 Å |
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Jul 21, 2016 |
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: 2.17→57.89 Å / Num. obs: 19876 / % possible obs: 100 % / Observed criterion σ(I): 2 / Redundancy: 3.8 % / CC1/2: 0.99 / Rmerge(I) obs: 0.245 / Rpim(I) all: 0.095 / Rrim(I) all: 0.263 / Net I/σ(I): 8 |
Reflection shell | Resolution: 2.17→2.24 Å / Redundancy: 7.7 % / Rmerge(I) obs: 1.216 / Mean I/σ(I) obs: 2 / Num. unique obs: 1698 / CC1/2: 0.663 / Rpim(I) all: 0.463 / Rrim(I) all: 1.303 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 3H9R Resolution: 2.17→57.89 Å / Data cutoff high absF: 2 / Cross valid method: FREE R-VALUE
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Refinement step | Cycle: LAST / Resolution: 2.17→57.89 Å
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