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Yorodumi- PDB-8ai7: Structure of carbamoylated human butyrylcholinesterase upon react... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8ai7 | ||||||
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Title | Structure of carbamoylated human butyrylcholinesterase upon reaction with 3-(((2-cycloheptylethyl)(methyl)amino)methyl)-1H-indol-7-yl N,N-dimethylcarbamate | ||||||
Components | Cholinesterase | ||||||
Keywords | HYDROLASE / Butyrylcholinesterase / Complex / Inhibitor / Carbamate | ||||||
Function / homology | Function and homology information cholinesterase / cocaine metabolic process / neuroblast differentiation / Neurotransmitter clearance / choline metabolic process / choline binding / response to folic acid / response to alkaloid / acetylcholine catabolic process / negative regulation of synaptic transmission ...cholinesterase / cocaine metabolic process / neuroblast differentiation / Neurotransmitter clearance / choline metabolic process / choline binding / response to folic acid / response to alkaloid / acetylcholine catabolic process / negative regulation of synaptic transmission / cholinesterase activity / peptide hormone processing / acetylcholinesterase activity / hydrolase activity, acting on ester bonds / nuclear envelope lumen / Aspirin ADME / Synthesis of PC / Synthesis, secretion, and deacylation of Ghrelin / catalytic activity / response to glucocorticoid / xenobiotic metabolic process / learning / amyloid-beta binding / blood microparticle / negative regulation of cell population proliferation / endoplasmic reticulum lumen / enzyme binding / extracellular space / extracellular region / identical protein binding / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.13 Å | ||||||
Authors | Brazzolotto, X. / Meden, A. / Knez, D. / Gobec, S. / Nachon, F. | ||||||
Funding support | France, 1items
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Citation | Journal: Eur.J.Med.Chem. / Year: 2023 Title: Pseudo-irreversible butyrylcholinesterase inhibitors: Structure-activity relationships, computational and crystallographic study of the N-dialkyl O-arylcarbamate warhead. Authors: Meden, A. / Knez, D. / Brazzolotto, X. / Modeste, F. / Perdih, A. / Pislar, A. / Zorman, M. / Zorovic, M. / Denic, M. / Pajk, S. / Zivin, M. / Nachon, F. / Gobec, S. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8ai7.cif.gz | 287.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8ai7.ent.gz | 194.1 KB | Display | PDB format |
PDBx/mmJSON format | 8ai7.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ai/8ai7 ftp://data.pdbj.org/pub/pdb/validation_reports/ai/8ai7 | HTTPS FTP |
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-Related structure data
Related structure data | 1p0iS S: Starting model for refinement |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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Components on special symmetry positions |
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-Components
-Protein , 1 types, 1 molecules F
#1: Protein | Mass: 59784.582 Da / Num. of mol.: 1 Mutation: N17Q, N455Q, N481Q, N486Q enginered mutations compared to mature wild type sequence to avoid too much N-glycozylation. Numeration on the maturated enzyme (devoid of the signal peptide) Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BCHE, CHE1 / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: P06276, cholinesterase |
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-Sugars , 3 types, 6 molecules
#2: Polysaccharide | Source method: isolated from a genetically manipulated source #3: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta- ...2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose | Source method: isolated from a genetically manipulated source #8: Sugar | |
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-Non-polymers , 6 types, 218 molecules
#4: Chemical | #5: Chemical | ChemComp-CL / #6: Chemical | ChemComp-NA / | #7: Chemical | ChemComp-M8X / | #9: Chemical | ChemComp-GOL / #10: Water | ChemComp-HOH / | |
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-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: 3.2 Å3/Da / Density % sol: 61.6 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / Details: Ammonium Sulfate |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: ESRF / Beamline: ID23-1 / Wavelength: 0.8856 Å |
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Oct 21, 2021 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.8856 Å / Relative weight: 1 |
Reflection | Resolution: 2.13→49.34 Å / Num. obs: 42424 / % possible obs: 98.17 % / Redundancy: 6.8 % / Biso Wilson estimate: 51.8 Å2 / CC1/2: 0.997 / Rmerge(I) obs: 0.08928 / Rpim(I) all: 0.03594 / Rrim(I) all: 0.09654 / Net I/σ(I): 10.97 |
Reflection shell | Resolution: 2.13→2.21 Å / Redundancy: 6.9 % / Rmerge(I) obs: 1.659 / Mean I/σ(I) obs: 1.12 / Num. unique obs: 4165 / CC1/2: 0.485 / Rpim(I) all: 0.6663 / Rrim(I) all: 1.794 / % possible all: 97.55 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 1p0i Resolution: 2.13→49.34 Å / SU ML: 0.2858 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 24.8646 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: 65.82 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.13→49.34 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: 16.8874562071 Å / Origin y: 32.1877996498 Å / Origin z: 38.8961206893 Å
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Refinement TLS group | Selection details: chain 'F' |