+Open data
-Basic information
Entry | Database: PDB / ID: 5he0 | ||||||||||||||||||
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Title | Bovine GRK2 in complex with Gbetagamma subunits and CCG215022 | ||||||||||||||||||
Components |
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Keywords | TRANSFERASE/TRANSFERASE INHIBITOR / RGS / kinase / PH / WD-40 / inhibitor complex / TRANSFERASE-TRANSFERASE INHIBITOR complex | ||||||||||||||||||
Function / homology | Function and homology information Calmodulin induced events / beta-adrenergic-receptor kinase / negative regulation of the force of heart contraction by chemical signal / negative regulation of relaxation of smooth muscle / Activation of SMO / beta-adrenergic receptor kinase activity / G protein-coupled receptor kinase activity / Edg-2 lysophosphatidic acid receptor binding / alpha-2A adrenergic receptor binding / negative regulation of striated muscle contraction ...Calmodulin induced events / beta-adrenergic-receptor kinase / negative regulation of the force of heart contraction by chemical signal / negative regulation of relaxation of smooth muscle / Activation of SMO / beta-adrenergic receptor kinase activity / G protein-coupled receptor kinase activity / Edg-2 lysophosphatidic acid receptor binding / alpha-2A adrenergic receptor binding / negative regulation of striated muscle contraction / desensitization of G protein-coupled receptor signaling pathway / positive regulation of protein localization to cilium / Cargo recognition for clathrin-mediated endocytosis / regulation of the force of heart contraction / positive regulation of smoothened signaling pathway / G protein-coupled receptor internalization / G alpha (s) signalling events / G alpha (q) signalling events / regulation of signal transduction / cardiac muscle contraction / cell projection / G protein-coupled receptor binding / intracellular protein transport / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G-protein activation / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / presynapse / GTPase binding / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / postsynapse / G alpha (q) signalling events / peptidyl-serine phosphorylation / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / protein kinase activity / G protein-coupled receptor signaling pathway / lysosomal membrane / protein phosphorylation / GTPase activity / synapse / protein-containing complex binding / signal transduction / extracellular exosome / ATP binding / membrane / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||||||||||||||
Biological species | Bos taurus (cattle) Homo sapiens (human) | ||||||||||||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.56 Å | ||||||||||||||||||
Authors | Cato, M.C. / Waninger-Saroni, J. / Tesmer, J.J.G. | ||||||||||||||||||
Funding support | United States, 5items
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Citation | Journal: J.Med.Chem. / Year: 2016 Title: Structure-Based Design, Synthesis, and Biological Evaluation of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors. Authors: Waldschmidt, H.V. / Homan, K.T. / Cruz-Rodriguez, O. / Cato, M.C. / Waninger-Saroni, J. / Larimore, K.M. / Cannavo, A. / Song, J. / Cheung, J.Y. / Kirchhoff, P.D. / Koch, W.J. / Tesmer, J.J. / Larsen, S.D. | ||||||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5he0.cif.gz | 423 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5he0.ent.gz | 346.4 KB | Display | PDB format |
PDBx/mmJSON format | 5he0.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/he/5he0 ftp://data.pdbj.org/pub/pdb/validation_reports/he/5he0 | HTTPS FTP |
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-Related structure data
Related structure data | 5he1C 5he2C 5he3C 4pnkS C: citing same article (ref.) 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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Unit cell |
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-Components
#1: Protein | Mass: 74762.086 Da / Num. of mol.: 1 / Fragment: UNP residues 30-670 / Mutation: S670A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Bos taurus (cattle) / Gene: ADRBK1, GRK2 / Plasmid: pFastBacDual / Production host: Trichoplusia ni (cabbage looper) References: UniProt: P21146, beta-adrenergic-receptor kinase |
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#2: Protein | Mass: 37285.734 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNB1 / Plasmid: pFastBacDual / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P62873 |
#3: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNG2 / Plasmid: pFastBacDual / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P59768 |
#4: Chemical | ChemComp-453 / ( |
#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: 3.47 Å3/Da / Density % sol: 64.51 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 6 Details: 50 mM MES, 0.8-1.2 M sodium chloride, 8-16% PEG3350 |
-Data collection
Diffraction | Mean temperature: 100 K | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 21-ID-G / Wavelength: 0.97857 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Jul 16, 2015 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Monochromator: diamond(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.97857 Å / Relative weight: 1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.6→30 Å / Num. obs: 47002 / % possible obs: 97 % / Redundancy: 3.5 % / Rmerge(I) obs: 0.067 / Rpim(I) all: 0.04 / Rrim(I) all: 0.078 / Χ2: 1.587 / Net I/av σ(I): 25.828 / Net I/σ(I): 12.6 / Num. measured all: 162451 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1 / Rejects: 0
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4PNK Resolution: 2.56→30 Å / Cor.coef. Fo:Fc: 0.949 / Cor.coef. Fo:Fc free: 0.91 / WRfactor Rfree: 0.2609 / WRfactor Rwork: 0.2007 / FOM work R set: 0.7682 / SU B: 27.119 / SU ML: 0.261 / SU R Cruickshank DPI: 0.4502 / SU Rfree: 0.3011 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.45 / ESU R Free: 0.301 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 163.33 Å2 / Biso mean: 71.102 Å2 / Biso min: 37.24 Å2
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Refinement step | Cycle: final / Resolution: 2.56→30 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.56→2.626 Å / Total num. of bins used: 20
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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