+Open data
-Basic information
Entry | Database: PDB / ID: 6u36 | ||||||
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Title | PCSK9 in complex with a Fab and compound 14 | ||||||
Components |
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Keywords | HYDROLASE/Immune System / Serine Type Endopeptidase Activity Proteolysis / HYDROLASE / HYDROLASE-Immune System 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 / PCSK9-LDLR complex / very-low-density lipoprotein particle binding / 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 / PCSK9-LDLR complex / very-low-density lipoprotein particle binding / 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 / signaling receptor inhibitor activity / LDL clearance / positive regulation of low-density lipoprotein particle receptor catabolic process / lipoprotein metabolic process / 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 / positive regulation of receptor internalization / apolipoprotein binding / 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 / kidney development / cholesterol homeostasis / Post-translational protein phosphorylation / neuron differentiation / cellular response to insulin stimulus / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / positive regulation of neuron apoptotic process / late endosome / early endosome / lysosome / endoplasmic reticulum lumen / lysosomal membrane / serine-type endopeptidase activity / apoptotic process / perinuclear region of cytoplasm / Golgi apparatus / cell surface / endoplasmic reticulum / RNA binding / extracellular space / extracellular region / plasma membrane / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.7 Å | ||||||
Authors | Lu, J. / Soisson, S. | ||||||
Citation | Journal: Cell Chem Biol / Year: 2020 Title: From Screening to Targeted Degradation: Strategies for the Discovery and Optimization of Small Molecule Ligands for PCSK9. Authors: Petrilli, W.L. / Adam, G.C. / Erdmann, R.S. / Abeywickrema, P. / Agnani, V. / Ai, X. / Baysarowich, J. / Byrne, N. / Caldwell, J.P. / Chang, W. / DiNunzio, E. / Feng, Z. / Ford, R. / Ha, S. ...Authors: Petrilli, W.L. / Adam, G.C. / Erdmann, R.S. / Abeywickrema, P. / Agnani, V. / Ai, X. / Baysarowich, J. / Byrne, N. / Caldwell, J.P. / Chang, W. / DiNunzio, E. / Feng, Z. / Ford, R. / Ha, S. / Huang, Y. / Hubbard, B. / Johnston, J.M. / Kavana, M. / Lisnock, J.M. / Liang, R. / Lu, J. / Lu, Z. / Meng, J. / Orth, P. / Palyha, O. / Parthasarathy, G. / Salowe, S.P. / Sharma, S. / Shipman, J. / Soisson, S.M. / Strack, A.M. / Youm, H. / Zhao, K. / Zink, D.L. / Zokian, H. / Addona, G.H. / Akinsanya, K. / Tata, J.R. / Xiong, Y. / Imbriglio, J.E. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6u36.cif.gz | 194.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6u36.ent.gz | 151.9 KB | Display | PDB format |
PDBx/mmJSON format | 6u36.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/u3/6u36 ftp://data.pdbj.org/pub/pdb/validation_reports/u3/6u36 | HTTPS FTP |
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-Related 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: 76081.656 Da / Num. of mol.: 2 / Mutation: V474I, G670E Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PCSK9, NARC1, PSEC0052 / Cell line (production host): HEK293 / Production host: Homo sapiens (human) References: UniProt: Q8NBP7, Hydrolases; Acting on peptide bonds (peptidases); Serine endopeptidases #2: Antibody | | Mass: 26546.590 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli) #3: Antibody | | Mass: 23437.020 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli) #4: Chemical | ChemComp-PVM / | #5: Water | ChemComp-HOH / | 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: 4.97 Å3/Da / Density % sol: 75.24 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion / Details: 0.1M Bicine pH9.0, 2% dioxane, 10% PEG 20000 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: CLSI / Beamline: 08ID-1 / Wavelength: 1 Å |
Detector | Type: MARMOSAIC 300 mm CCD / Detector: CCD / Date: May 21, 2011 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.7→50 Å / Num. obs: 57636 / % possible obs: 100 % / Redundancy: 7.7 % / Rmerge(I) obs: 0.074 / Net I/σ(I): 26.5 |
Reflection shell | Resolution: 2.7→2.8 Å / Rmerge(I) obs: 0.583 / Num. unique obs: 5756 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.7→36.67 Å / Cor.coef. Fo:Fc: 0.916 / Cor.coef. Fo:Fc free: 0.904 / SU R Cruickshank DPI: 0.331 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.31 / SU Rfree Blow DPI: 0.232 / SU Rfree Cruickshank DPI: 0.242
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Displacement parameters | Biso max: 130.34 Å2 / Biso mean: 73.79 Å2 / Biso min: 46.68 Å2
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Refine analyze | Luzzati coordinate error obs: 0.43 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.7→36.67 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.7→2.72 Å / Total num. of bins used: 50
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