[English] 日本語
Yorodumi
- PDB-6ezh: Torpedo californica AChE in complex with indolic multi-target dir... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6ezh
TitleTorpedo californica AChE in complex with indolic multi-target directed ligand
ComponentsAcetylcholinesterase
KeywordsHYDROLASE / Acetylcholinesterase / Multi-target inhibitor / Alzheimer desease
Function / homology
Function and homology information


acetylcholine catabolic process in synaptic cleft / acetylcholinesterase / choline metabolic process / acetylcholinesterase activity / side of membrane / synaptic cleft / synapse / : / plasma membrane
Similarity search - Function
Acetylcholinesterase, fish/snake / : / Cholinesterase / Carboxylesterase type B, active site / Carboxylesterases type-B serine active site. / Carboxylesterase type B, conserved site / Carboxylesterases type-B signature 2. / Carboxylesterase, type B / Carboxylesterase family / Alpha/Beta hydrolase fold, catalytic domain ...Acetylcholinesterase, fish/snake / : / Cholinesterase / Carboxylesterase type B, active site / Carboxylesterases type-B serine active site. / Carboxylesterase type B, conserved site / Carboxylesterases type-B signature 2. / Carboxylesterase, type B / Carboxylesterase family / Alpha/Beta hydrolase fold, catalytic domain / Alpha/Beta hydrolase fold / Rossmann fold / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
Chem-C6H / Acetylcholinesterase
Similarity search - Component
Biological speciesTetronarce californica (Pacific electric ray)
MethodX-RAY DIFFRACTION / SYNCHROTRON / Resolution: 2.6 Å
AuthorsSantoni, G. / Lalut, J. / Karila, D. / Lecoutey, C. / Davis, A. / Nachon, F. / Sillman, I. / Sussman, J. / Weik, M. / Maurice, T. ...Santoni, G. / Lalut, J. / Karila, D. / Lecoutey, C. / Davis, A. / Nachon, F. / Sillman, I. / Sussman, J. / Weik, M. / Maurice, T. / Dallemagne, P. / Rochais, C.
CitationJournal: Eur J Med Chem / Year: 2018
Title: Novel multitarget-directed ligands targeting acetylcholinesterase and sigma1receptors as lead compounds for treatment of Alzheimer's disease: Synthesis, evaluation, and structural ...Title: Novel multitarget-directed ligands targeting acetylcholinesterase and sigma1receptors as lead compounds for treatment of Alzheimer's disease: Synthesis, evaluation, and structural characterization of their complexes with acetylcholinesterase.
Authors: Lalut, J. / Santoni, G. / Karila, D. / Lecoutey, C. / Davis, A. / Nachon, F. / Silman, I. / Sussman, J. / Weik, M. / Maurice, T. / Dallemagne, P. / Rochais, C.
History
DepositionNov 15, 2017Deposition site: PDBE / Processing site: PDBE
Revision 1.0Nov 21, 2018Provider: repository / Type: Initial release
Revision 1.1Nov 28, 2018Group: Data collection / Database references / Category: citation / citation_author / pdbx_database_proc
Item: _citation.journal_abbrev / _citation.journal_id_ISSN ..._citation.journal_abbrev / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.name
Revision 1.2Jul 29, 2020Group: Data collection / Derived calculations / Structure summary
Category: chem_comp / entity ...chem_comp / entity / pdbx_chem_comp_identifier / pdbx_entity_nonpoly / struct_conn / struct_site / struct_site_gen
Item: _chem_comp.name / _chem_comp.type ..._chem_comp.name / _chem_comp.type / _entity.pdbx_description / _pdbx_entity_nonpoly.name / _struct_conn.pdbx_role
Description: Carbohydrate remediation / Provider: repository / Type: Remediation
Revision 1.3Jan 17, 2024Group: Data collection / Database references ...Data collection / Database references / Refinement description / Structure summary
Category: chem_comp / chem_comp_atom ...chem_comp / chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _chem_comp.pdbx_synonyms / _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.4Nov 13, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Acetylcholinesterase
B: Acetylcholinesterase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)123,1928
Polymers121,4732
Non-polymers1,7196
Water9,908550
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2630 Å2
ΔGint1 kcal/mol
Surface area38920 Å2
MethodPISA
Unit cell
Length a, b, c (Å)91.440, 106.740, 150.750
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Acetylcholinesterase / AChE


Mass: 60736.516 Da / Num. of mol.: 2 / Source method: isolated from a natural source
Source: (natural) Tetronarce californica (Pacific electric ray)
References: UniProt: P04058, acetylcholinesterase
#2: Sugar
ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0
#3: Chemical ChemComp-C6H / 1-(7-chloranyl-4-methoxy-1~{H}-indol-5-yl)-3-[1-(cyclohexylmethyl)piperidin-4-yl]propan-1-one / MR28926


Mass: 416.984 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C24H33ClN2O2 / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 550 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 3.03 Å3/Da / Density % sol: 59.38 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / Details: 36% PEG 200 150mM MES pH 5.6

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID14-4 / Wavelength: 0.939 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Jul 28, 2013
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.939 Å / Relative weight: 1
ReflectionResolution: 2.6→46.09 Å / Num. obs: 45936 / % possible obs: 99.72 % / Redundancy: 4.49 % / Net I/σ(I): 8.43
Reflection shellResolution: 2.6→2.67 Å

-
Processing

Software
NameVersionClassification
REFMAC5.8.0107refinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing
RefinementStarting model: 1ea5

1ea5


Resolution: 2.6→46.09 Å / Cor.coef. Fo:Fc: 0.934 / Cor.coef. Fo:Fc free: 0.901 / Cross valid method: THROUGHOUT / ESU R: 0.632 / ESU R Free: 0.326 / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.27315 1379 3 %RANDOM
Rwork0.22192 ---
obs0.22342 44557 99.7 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso mean: 13.113 Å2
Baniso -1Baniso -2Baniso -3
1--1.61 Å20 Å2-0 Å2
2--5.28 Å2-0 Å2
3----3.67 Å2
Refinement stepCycle: 1 / Resolution: 2.6→46.09 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8488 0 114 570 9172
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0090.0198876
X-RAY DIFFRACTIONr_bond_other_d00.028115
X-RAY DIFFRACTIONr_angle_refined_deg1.2711.95712059
X-RAY DIFFRACTIONr_angle_other_deg3.976318693
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.20451064
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.94223.995423
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.545151415
X-RAY DIFFRACTIONr_dihedral_angle_4_deg17.3661549
X-RAY DIFFRACTIONr_chiral_restr0.0850.21257
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.02110081
X-RAY DIFFRACTIONr_gen_planes_other0.0080.022148
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it3.1261.2674259
X-RAY DIFFRACTIONr_mcbond_other3.1191.2674258
X-RAY DIFFRACTIONr_mcangle_it4.1621.8815322
X-RAY DIFFRACTIONr_mcangle_other4.1651.8825323
X-RAY DIFFRACTIONr_scbond_it4.7791.4024617
X-RAY DIFFRACTIONr_scbond_other4.7541.3824554
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other5.8431.9846650
X-RAY DIFFRACTIONr_long_range_B_refined6.0310.50210880
X-RAY DIFFRACTIONr_long_range_B_other5.92310.21110602
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.6→2.668 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.363 100 -
Rwork0.294 3229 -
obs--99.85 %

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more