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- PDB-7k7z: Structure of a hit for G Protein Coupled Receptor Kinase 2 (GRK2)... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7k7z | ||||||
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Title | Structure of a hit for G Protein Coupled Receptor Kinase 2 (GRK2) Inhibitor for the Potential Treatment of Heart Failure | ||||||
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![]() | SIGNALING PROTEIN / TRANSFERASE/INHIBITOR / serine/threonine protein kinase / TRANSFERASE-INHIBITOR complex | ||||||
Function / homology | ![]() beta-adrenergic-receptor kinase / negative regulation of the force of heart contraction by chemical signal / negative regulation of relaxation of smooth muscle / beta-adrenergic receptor kinase activity / G protein-coupled receptor kinase activity / Edg-2 lysophosphatidic acid receptor binding / alpha-2A adrenergic receptor binding / tachykinin receptor signaling pathway / positive regulation of catecholamine secretion / Activation of SMO ...beta-adrenergic-receptor kinase / negative regulation of the force of heart contraction by chemical signal / negative regulation of relaxation of smooth muscle / beta-adrenergic receptor kinase activity / G protein-coupled receptor kinase activity / Edg-2 lysophosphatidic acid receptor binding / alpha-2A adrenergic receptor binding / tachykinin receptor signaling pathway / positive regulation of catecholamine secretion / Activation of SMO / negative regulation of striated muscle contraction / desensitization of G protein-coupled receptor signaling pathway / regulation of the force of heart contraction / Calmodulin induced events / cardiac muscle contraction / viral genome replication / G protein-coupled receptor binding / 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-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / receptor internalization / cilium / 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) / Cargo recognition for clathrin-mediated endocytosis / GTPase binding / retina development in camera-type eye / presynapse / Ca2+ pathway / heart development / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / peptidyl-serine phosphorylation / Ras protein signal transduction / postsynapse / cell population proliferation / Extra-nuclear estrogen signaling / protein kinase activity / symbiont entry into host cell / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / protein-containing complex binding / signal transduction / extracellular exosome / ATP binding / membrane / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Spurlino, J.C. / Milligan, C. | ||||||
![]() | ![]() Title: Hit-to-lead optimization and discovery of a potent, and orally bioavailable G protein coupled receptor kinase 2 (GRK2) inhibitor. Authors: Xu, G. / Gaul, M.D. / Liu, Z. / DesJarlais, R.L. / Qi, J. / Wang, W. / Krosky, D. / Petrounia, I. / Milligan, C.M. / Hermans, A. / Lu, H.R. / Huang, D.Z. / Xu, J.Z. / Spurlino, J.C. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 505.3 KB | Display | ![]() |
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PDB format | ![]() | 346.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
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Links
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Assembly
Deposited unit | ![]()
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Unit cell |
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Components
#1: Protein | Mass: 74545.641 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() References: UniProt: P25098, 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.) ![]() ![]() |
#3: Protein | Mass: 6519.523 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#4: Chemical | ChemComp-W4G / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 3.04 Å3/Da / Density % sol: 59.5 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion / pH: 6.5 / Details: 2% PEG 3350, 0.1M MES pH 6.5, 0.2M NaCl |
-Data collection
Diffraction | Mean temperature: 80 K / Serial crystal experiment: N |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS PILATUS 2M / Detector: PIXEL / Date: Oct 13, 2014 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.6→50 Å / Num. obs: 43160 / % possible obs: 99.2 % / Redundancy: 3.4 % / Biso Wilson estimate: 52.338872052 Å2 / Rmerge(I) obs: 0.081 / Rpim(I) all: 0.073 / Net I/σ(I): 9.96 |
Reflection shell | Resolution: 2.6→2.64 Å / Num. unique obs: 2147 / CC1/2: 0.577 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: GRK2 Resolution: 2.60608692764→37.1456237759 Å / SU ML: 0.3874797241 / Cross valid method: THROUGHOUT / σ(F): 1.33786888298 / Phase error: 30.7403996444 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 72.4782885558 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.60608692764→37.1456237759 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Origin x: -9.87793689179 Å / Origin y: 13.7000030771 Å / Origin z: 29.03458561 Å
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Refinement TLS group | Selection details: all |