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- PDB-7w41: Crystal Structure of Human Gastrin Releasing Peptide Receptor in ... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7w41 | |||||||||||||||||||||
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Title | Crystal Structure of Human Gastrin Releasing Peptide Receptor in complex with the antagonist PD176252 | |||||||||||||||||||||
![]() | Gastrin-releasing peptide receptor,GlgA glycogen synthase | |||||||||||||||||||||
![]() | MEMBRANE PROTEIN / GPCR / Gastrin Releasing Peptide Receptor | |||||||||||||||||||||
Function / homology | ![]() response to external biotic stimulus / positive regulation of respiratory gaseous exchange / positive regulation of behavioral fear response / neuropeptide receptor activity / glycogen (starch) synthase activity / psychomotor behavior / neuropeptide binding / G protein-coupled peptide receptor activity / glycogen biosynthetic process / motor behavior ...response to external biotic stimulus / positive regulation of respiratory gaseous exchange / positive regulation of behavioral fear response / neuropeptide receptor activity / glycogen (starch) synthase activity / psychomotor behavior / neuropeptide binding / G protein-coupled peptide receptor activity / glycogen biosynthetic process / motor behavior / social behavior / Peptide ligand-binding receptors / phospholipase C-activating G protein-coupled receptor signaling pathway / regulation of cell population proliferation / G alpha (q) signalling events / learning or memory / G protein-coupled receptor signaling pathway / plasma membrane / cytosol Similarity search - Function | |||||||||||||||||||||
Biological species | ![]() ![]() ![]() | |||||||||||||||||||||
Method | ![]() ![]() ![]() | |||||||||||||||||||||
![]() | Peng, S. / Zhan, Y. / Zhang, H. | |||||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structures of human gastrin-releasing peptide receptors bound to antagonist and agonist for cancer and itch therapy. Authors: Shuman Peng / Yuting Zhan / Dongqi Zhang / Lu Ren / Anqi Chen / Zhou-Feng Chen / Haitao Zhang / ![]() ![]() Abstract: Gastrin releasing peptide receptor (GRPR), a member of the bombesin (BBN) G protein-coupled receptors, is aberrantly overexpressed in several malignant tumors, including those of the breast, ...Gastrin releasing peptide receptor (GRPR), a member of the bombesin (BBN) G protein-coupled receptors, is aberrantly overexpressed in several malignant tumors, including those of the breast, prostate, pancreas, lung, and central nervous system. Additionally, it also mediates non-histaminergic itch and pathological itch conditions in mice. Thus, GRPR could be an attractive target for cancer and itch therapy. Here, we report the inactive state crystal structure of human GRPR in complex with the non-peptide antagonist PD176252, as well as two active state cryo-electron microscopy (cryo-EM) structures of GRPR bound to the endogenous peptide agonist gastrin-releasing peptide and the synthetic BBN analog [D-Phe, β-Ala, Phe, Nle] Bn (6-14), in complex with G heterotrimers. These structures revealed the molecular mechanisms for the ligand binding, receptor activation, and G proteins signaling of GRPR, which are expected to accelerate the structure-based design of GRPR antagonists and agonists for the treatments of cancer and pruritus. | |||||||||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 112.1 KB | Display | ![]() |
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PDB format | ![]() | 82.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 727.7 KB | Display | ![]() |
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Full document | ![]() | 736 KB | Display | |
Data in XML | ![]() | 19.1 KB | Display | |
Data in CIF | ![]() | 25.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7w3zC ![]() 7w40C ![]() 7f6gS S: Starting model for refinement C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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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: 54374.758 Da / Num. of mol.: 1 / Mutation: S127K,I157A,R259E Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() Gene: GRPR, PAB2292 / Strain: GE5 / Orsay / Production host: ![]() ![]() |
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#2: Chemical | ChemComp-8B8 / ( |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 3.34 Å3/Da / Density % sol: 57.4 % |
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Crystal grow | Temperature: 294 K / Method: lipidic cubic phase / pH: 6.8 Details: 100mM MES, pH 6.8, 300mM Ammonium dihydrogen phosphate, 28% PEG 400, 5% polypropylene glycol P 400 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: PSI PILATUS 6M / Detector: PIXEL / Date: Nov 14, 2021 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.033 Å / Relative weight: 1 |
Reflection | Resolution: 2.95→27.767 Å / Num. obs: 14852 / % possible obs: 96.9 % / Redundancy: 4 % / Rmerge(I) obs: 0.151 / Net I/σ(I): 8.14 |
Reflection shell | Resolution: 2.95→3.06 Å / Rmerge(I) obs: 0.599 / Num. unique obs: 1449 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 7F6G Resolution: 2.952→27.767 Å / Cor.coef. Fo:Fc: 0.907 / Cor.coef. Fo:Fc free: 0.878 / SU B: 0.1 / SU ML: 0 / Cross valid method: FREE R-VALUE / ESU R: 0.465 / ESU R Free: 0.532 Details: Hydrogens have been added in their 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 BULK SOLVENT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 70 Å2
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Refinement step | Cycle: LAST / Resolution: 2.952→27.767 Å
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LS refinement shell |
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