+Open data
-Basic information
Entry | Database: PDB / ID: 7s5g | |||||||||
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Title | PCSK9 in complex with compound 19 | |||||||||
Components |
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Keywords | PROTEIN BINDING / HYDROLASE / cholesterol / LDL receptor / EGFA domain | |||||||||
Function / homology | Function and homology information negative regulation of low-density lipoprotein particle receptor binding / negative regulation of receptor-mediated endocytosis involved in cholesterol transport / low-density lipoprotein particle receptor catabolic process / extrinsic component of external side of plasma membrane / very-low-density lipoprotein particle binding / PCSK9-LDLR complex / negative regulation of receptor recycling / PCSK9-AnxA2 complex / negative regulation of sodium ion transmembrane transporter activity / apolipoprotein receptor binding ...negative regulation of low-density lipoprotein particle receptor binding / negative regulation of receptor-mediated endocytosis involved in cholesterol transport / low-density lipoprotein particle receptor catabolic process / extrinsic component of external side of plasma membrane / very-low-density lipoprotein particle binding / PCSK9-LDLR complex / negative regulation of receptor recycling / PCSK9-AnxA2 complex / negative regulation of sodium ion transmembrane transporter activity / apolipoprotein receptor binding / negative regulation of low-density lipoprotein particle clearance / low-density lipoprotein particle binding / LDL clearance / positive regulation of low-density lipoprotein particle receptor catabolic process / lipoprotein metabolic process / signaling receptor inhibitor activity / very-low-density lipoprotein particle receptor binding / negative regulation of low-density lipoprotein receptor activity / negative regulation of receptor internalization / endolysosome membrane / regulation of signaling receptor activity / sodium channel inhibitor activity / lysosomal transport / triglyceride metabolic process / low-density lipoprotein particle receptor binding / COPII-coated ER to Golgi transport vesicle / apolipoprotein binding / positive regulation of receptor internalization / protein autoprocessing / Hydrolases; Acting on peptide bonds (peptidases); Serine endopeptidases / phospholipid metabolic process / regulation of neuron apoptotic process / VLDLR internalisation and degradation / cellular response to starvation / cholesterol metabolic process / neurogenesis / liver development / cholesterol homeostasis / kidney development / Post-translational protein phosphorylation / neuron differentiation / cellular response to insulin stimulus / positive regulation of neuron apoptotic process / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / : / late endosome / lysosome / early endosome / lysosomal membrane / endoplasmic reticulum lumen / serine-type endopeptidase activity / apoptotic process / perinuclear region of cytoplasm / Golgi apparatus / cell surface / endoplasmic reticulum / extracellular space / RNA binding / extracellular region / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) synthetic construct (others) | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.041 Å | |||||||||
Authors | Orth, P. | |||||||||
Funding support | 1items
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Citation | Journal: J.Med.Chem. / Year: 2021 Title: A Series of Novel, Highly Potent, and Orally Bioavailable Next-Generation Tricyclic Peptide PCSK9 Inhibitors. Authors: Tucker, T.J. / Embrey, M.W. / Alleyne, C. / Amin, R.P. / Bass, A. / Bhatt, B. / Bianchi, E. / Branca, D. / Bueters, T. / Buist, N. / Ha, S.N. / Hafey, M. / He, H. / Higgins, J. / Johns, D.G. ...Authors: Tucker, T.J. / Embrey, M.W. / Alleyne, C. / Amin, R.P. / Bass, A. / Bhatt, B. / Bianchi, E. / Branca, D. / Bueters, T. / Buist, N. / Ha, S.N. / Hafey, M. / He, H. / Higgins, J. / Johns, D.G. / Kerekes, A.D. / Koeplinger, K.A. / Kuethe, J.T. / Li, N. / Murphy, B. / Orth, P. / Salowe, S. / Shahripour, A. / Tracy, R. / Wang, W. / Wu, C. / Xiong, Y. / Zokian, H.J. / Wood, H.B. / Walji, A. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7s5g.cif.gz | 96.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7s5g.ent.gz | 68.3 KB | Display | PDB format |
PDBx/mmJSON format | 7s5g.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/s5/7s5g ftp://data.pdbj.org/pub/pdb/validation_reports/s5/7s5g | HTTPS FTP |
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-Related structure data
Related structure data | 7s5hC 2w2mS 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
-Protein , 2 types, 2 molecules AB
#1: Protein | Mass: 13791.463 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PCSK9, NARC1, PSEC0052 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: Q8NBP7, Hydrolases; Acting on peptide bonds (peptidases); Serine endopeptidases |
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#2: Protein | Mass: 32836.910 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PCSK9, NARC1, PSEC0052 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: Q8NBP7, Hydrolases; Acting on peptide bonds (peptidases); Serine endopeptidases |
-Protein/peptide , 1 types, 1 molecules C
#3: Protein/peptide | Mass: 1265.515 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
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-Non-polymers , 3 types, 128 molecules
#4: Chemical | ChemComp-GOL / |
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#5: Chemical | ChemComp-89N / ( |
#6: Water | ChemComp-HOH / |
-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.34 Å3/Da / Density % sol: 47.35 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, sitting drop / pH: 6 / Details: 20% PEG3350, 200mM CaCl2, 100mM MES pH 6 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Mar 30, 2016 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.041→61.51 Å / Num. obs: 21355 / % possible obs: 84.7 % / Redundancy: 9.6 % / CC1/2: 0.993 / Net I/σ(I): 7.2 |
Reflection shell | Resolution: 2.041→2.181 Å / Num. unique obs: 1069 / CC1/2: 0.51 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 2W2M Resolution: 2.041→61.51 Å / Cor.coef. Fo:Fc: 0.918 / Cor.coef. Fo:Fc free: 0.877 / SU R Cruickshank DPI: 0.299 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.31 / SU Rfree Blow DPI: 0.246 / SU Rfree Cruickshank DPI: 0.245
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Displacement parameters | Biso max: 63.74 Å2 / Biso mean: 26.68 Å2 / Biso min: 10.79 Å2
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Refine analyze | Luzzati coordinate error obs: 0.34 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.041→61.51 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.041→2.17 Å / Rfactor Rfree error: 0
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