+Open data
-Basic information
Entry | Database: PDB / ID: 6xib | |||||||||
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Title | PCSK9(deltaCRD) in complex with cyclic peptide 30 | |||||||||
Components |
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Keywords | HYDROLASE/INHIBITOR / protein-peptide complex / cyclic peptide / non-natural amino acids / HYDROLASE / HYDROLASE-INHIBITOR complex | |||||||||
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 / FOURIER SYNTHESIS / Resolution: 1.546 Å | |||||||||
Authors | Orth, P. | |||||||||
Citation | Journal: J.Med.Chem. / Year: 2020 Title: Series of Novel and Highly Potent Cyclic Peptide PCSK9 Inhibitors Derived from an mRNA Display Screen and Optimized via Structure-Based Design. Authors: Alleyne, C. / Amin, R.P. / Bhatt, B. / Bianchi, E. / Blain, J.C. / Boyer, N. / Branca, D. / Embrey, M.W. / Ha, S.N. / Jette, K. / Johns, D.G. / Kerekes, A.D. / Koeplinger, K.A. / LaPlaca, D. ...Authors: Alleyne, C. / Amin, R.P. / Bhatt, B. / Bianchi, E. / Blain, J.C. / Boyer, N. / Branca, D. / Embrey, M.W. / Ha, S.N. / Jette, K. / Johns, D.G. / Kerekes, A.D. / Koeplinger, K.A. / LaPlaca, D. / Li, N. / Murphy, B. / Orth, P. / Ricardo, A. / Salowe, S. / Seyb, K. / Shahripour, A. / Stringer, J.R. / Sun, Y. / Tracy, R. / Wu, C. / Xiong, Y. / Youm, H. / Zokian, H.J. / Tucker, T.J. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6xib.cif.gz | 100.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6xib.ent.gz | 72.5 KB | Display | PDB format |
PDBx/mmJSON format | 6xib.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/xi/6xib ftp://data.pdbj.org/pub/pdb/validation_reports/xi/6xib | HTTPS FTP |
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-Related structure data
Related structure data | 6xicC 6xidC 6xieC 6xifC 4nmxS 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: 13791.463 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PCSK9 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q8NBP7 |
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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 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q8NBP7 |
#3: Protein/peptide | Mass: 1521.711 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
#4: Chemical | ChemComp-GOL / |
#5: Water | ChemComp-HOH / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.59 Å3/Da / Density % sol: 52.56 % |
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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 PILATUS3 S 6M / Detector: PIXEL / Date: Dec 5, 2014 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 1.546→61.511 Å / Num. obs: 57785 / % possible obs: 92.7 % / Redundancy: 9.3 % / CC1/2: 0.998 / Net I/σ(I): 8.6 |
Reflection shell | Resolution: 1.546→1.631 Å / Num. unique obs: 2883 / CC1/2: 0.577 |
-Processing
Software |
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Refinement | Method to determine structure: FOURIER SYNTHESIS Starting model: 4NMX Resolution: 1.546→61.51 Å / Cor.coef. Fo:Fc: 0.952 / Cor.coef. Fo:Fc free: 0.95 / SU R Cruickshank DPI: 0.083 / Cross valid method: THROUGHOUT / SU R Blow DPI: 0.088 / SU Rfree Blow DPI: 0.082 / SU Rfree Cruickshank DPI: 0.079
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Displacement parameters | Biso mean: 24.28 Å2
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Refine analyze | Luzzati coordinate error obs: 0.22 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.546→61.51 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 1.55→1.59 Å
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