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Yorodumi- PDB-1h22: Structure of acetylcholinesterase (E.C. 3.1.1.7) complexed with (... -
+Open data
-Basic information
Entry | Database: PDB / ID: 1h22 | ||||||
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Title | Structure of acetylcholinesterase (E.C. 3.1.1.7) complexed with (S,S)-(-)-bis(10)-hupyridone at 2.15A resolution | ||||||
Components | ACETYLCHOLINESTERASE | ||||||
Keywords | HYDROLASE / SERINE HYDROLASE / ACETYLCHOLINESTERASE / NEUROTRANSMITTER CLEAVAGE / ALZHEIMER'S DISEASE / BIVALENT LIGAND / DUAL-SITE BINDING / INHIBITOR / HUPERZINE A / SERINE ESTERASE SYNAPSE / MEMBRANE / NERVE / MUSCLE / GPI-ANCHOR NEUROTRANSMITTER DEGRADATION / GLYCOPROTEIN / BIS(10)-HUPYRID | ||||||
Function / homology | Function and homology information acetylcholine catabolic process in synaptic cleft / acetylcholinesterase / acetylcholinesterase activity / choline metabolic process / side of membrane / synaptic cleft / synapse / extracellular space / plasma membrane Similarity search - Function | ||||||
Biological species | TORPEDO CALIFORNICA (Pacific electric ray) | ||||||
Method | X-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.15 Å | ||||||
Authors | Wong, D.M. / Greenblatt, H.M. / Carlier, P.R. / Han, Y.-F. / Pang, Y.-P. / Silman, I. / Sussman, J.L. | ||||||
Citation | Journal: J.Am.Chem.Soc. / Year: 2003 Title: Acetylcholinesterase Complexed with Bivalent Ligands Related to Huperzine A: Experimental Evidence for Species-Dependent Protein-Ligand Complementarity Authors: Wong, D.M. / Greenblatt, H.M. / Dvir, H. / Carlier, P.R. / Han, Y.-F. / Pang, Y.-P. / Silman, I. / Sussman, J.L. #1: Journal: Angew.Chem.Int.Ed.Engl. / Year: 2000 Title: Dimerization of an Inactive Fragment of Huperzine a Produces a Drug with Twice the Potency of the Natural Product Authors: Carlier, P.R. / Du, D.-M. / Han, Y.-F. / Liu, J. / Perola, E. / Williams, I.D. / Pang, Y.-P. #2: Journal: Nat.Struct.Biol. / Year: 1997 Title: Structure of Acetylcholinesterase Complexed with the Nootropic Alkaloid, (-)-Huperzine A Authors: Raves, M.L. / Harel, M. / Pang, Y.-P. / Silman, I. / Kozikowski, A.P. / Sussman, J.L. #3: Journal: J. Comput. Aided Mol. Des. / Year: 1994 Title: Prediction of the Binding Sites of Huperzine a in Acetylcholinesterase by Docking Studies Authors: Pang, Y.-P. / Kozikowski, A.P. #4: Journal: Science / Year: 1991 Title: Atomic Structure of Acetylcholinesterase from Torpedo Californica: A Prototypic Acetylcholine-Binding Protein Authors: Sussman, J.L. / Harel, M. / Frolow, F. / Oefner, C. / Goldman, A. / Toker, L. / Silman, I. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 1h22.cif.gz | 127.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb1h22.ent.gz | 97 KB | Display | PDB format |
PDBx/mmJSON format | 1h22.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 1h22_validation.pdf.gz | 701.4 KB | Display | wwPDB validaton report |
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Full document | 1h22_full_validation.pdf.gz | 712 KB | Display | |
Data in XML | 1h22_validation.xml.gz | 24.1 KB | Display | |
Data in CIF | 1h22_validation.cif.gz | 34.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/h2/1h22 ftp://data.pdbj.org/pub/pdb/validation_reports/h2/1h22 | HTTPS FTP |
-Related structure data
Related structure data | 1h23C 2aceS C: citing same article (ref.) S: Starting model for refinement |
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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: 61325.090 Da / Num. of mol.: 1 / Source method: isolated from a natural source Details: SYNTHETIC BIVALENT HUPA-LIKE DIMER, (S, S)-(-)-BIS(10)-HUPYRIDONE ((S, S)-(-)-N, N'-DI-5'- -[5', 6', 7', 8'-TETRAHYDRO-2'(1'H)-QUINOLINONYL] -1, 10-DIAMINODECANE) DIHYDROCHLORIDE, WITH ONE ...Details: SYNTHETIC BIVALENT HUPA-LIKE DIMER, (S, S)-(-)-BIS(10)-HUPYRIDONE ((S, S)-(-)-N, N'-DI-5'- -[5', 6', 7', 8'-TETRAHYDRO-2'(1'H)-QUINOLINONYL] -1, 10-DIAMINODECANE) DIHYDROCHLORIDE, WITH ONE MONOMER UNIT BOUND TO THE 'ANIONIC' SUBSITE, NEAR THE BOTTOM OF THE ACTIVE SITE GORGE, AND THE SECOND MONOMER UNIT BOUND TO THE 'PERIPHERAL' ANIONIC SITE AT THE TOP OF THE GORGE, THUS SPANNING THE ACTIVE SITE GORGE Source: (natural) TORPEDO CALIFORNICA (Pacific electric ray) Organ: ELECTRIC ORGAN / Variant: G2 FORM / Tissue: ELECTROPLAQUE / References: UniProt: P04058, acetylcholinesterase | ||||
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#2: Chemical | ChemComp-E10 / ( | ||||
#3: Sugar | #4: Water | ChemComp-HOH / | Compound details | COMPOUND HYDROLYZES CHOLINE RELEASED INTO THE SYNAPSE. CATALYTIC ACTIVITY: ACETYLCHOLINE + H(2)O = ...COMPOUND HYDROLYZES | |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 4.06 Å3/Da / Density % sol: 69.37 % | ||||||||||||||||||||||||||||||
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Crystal grow | Temperature: 277 K / pH: 5.8 Details: PROTEIN WAS CRYSTALLISED FROM 28-30% V/V PEG 200 0.5M MES PH 5.8 AT 4 DEG. CELSIUS; THEN SOAKED IN MOTHER LIQUOR (40% V/V PEG 200 IN 0.1 M MES BUFFER, PH 5.8) CONTAINING 2MM (S,S)-(-)-BIS(10) ...Details: PROTEIN WAS CRYSTALLISED FROM 28-30% V/V PEG 200 0.5M MES PH 5.8 AT 4 DEG. CELSIUS; THEN SOAKED IN MOTHER LIQUOR (40% V/V PEG 200 IN 0.1 M MES BUFFER, PH 5.8) CONTAINING 2MM (S,S)-(-)-BIS(10)-HUPYRIDONE DIHYDROCHLORIDE FOR ONE DAY. | ||||||||||||||||||||||||||||||
Crystal grow | *PLUS Temperature: 4 ℃ / Method: vapor diffusion, hanging drop | ||||||||||||||||||||||||||||||
Components of the solutions | *PLUS
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-Data collection
Diffraction | Mean temperature: 120 K |
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Diffraction source | Source: ROTATING ANODE / Type: RIGAKU RUH3R / Wavelength: 1.5418 |
Detector | Type: RIGAKU IMAGE PLATE / Detector: IMAGE PLATE / Date: Jan 7, 2001 / Details: OSMIC BLUE CONFOCAL MIRRORS |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1.5418 Å / Relative weight: 1 |
Reflection | Resolution: 2.15→26.4 Å / Num. obs: 53982 / % possible obs: 95.3 % / Redundancy: 4.7 % / Rmerge(I) obs: 0.049 / Net I/σ(I): 17.3 |
Reflection shell | Resolution: 2.15→2.23 Å / Redundancy: 10 % / Rmerge(I) obs: 0.228 / % possible all: 96.8 |
Reflection | *PLUS Num. all: 53982 / Num. obs: 51434 / Num. measured all: 447124 |
Reflection shell | *PLUS % possible obs: 96.8 % |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: PDB ENTRY 2ACE Resolution: 2.15→26.4 Å / Rfactor Rfree error: 0.004385 / Data cutoff high absF: 10000 / Cross valid method: THROUGHOUT / σ(F): 0 Details: SEVERAL RESIDUES ARE NOT SEEN IN THE CRYSTAL STRUCTURE, DUE TO DISORDER. THESE INCLUDE ASP A1, ASP A2, HIS A3 AND THE C-TERMINAL RESIDUES AFTER THR A535. SEVERAL RESIDUES MISSING IN CHAIN ...Details: SEVERAL RESIDUES ARE NOT SEEN IN THE CRYSTAL STRUCTURE, DUE TO DISORDER. THESE INCLUDE ASP A1, ASP A2, HIS A3 AND THE C-TERMINAL RESIDUES AFTER THR A535. SEVERAL RESIDUES MISSING IN CHAIN BREAK, FROM HIS A486 - GLU A489 (INCLUSIVE). TWO ALTERNATE SIDE CHAIN CONFORMATIONS WERE FITTED FOR THE RESIDUES LEU A143 (SET TO 50% OCCUPANCY EACH), AND ARG A243 (SET TO 80% AND 20% OCCUPANCY).
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Solvent computation | Solvent model: FLAT MODEL / Bsol: 56.6 Å2 / ksol: 0.383 e/Å3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 34.244 Å2
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Refinement step | Cycle: LAST / Resolution: 2.15→26.4 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.15→2.25 Å / Rfactor Rfree error: 0.0144 / Total num. of bins used: 8
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Xplor file |
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Refinement | *PLUS Rfactor obs: 0.19 / Rfactor Rfree: 0.221 / Rfactor Rwork: 0.19 / % reflection Rfree: 5 % | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | *PLUS | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | *PLUS | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints | *PLUS
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