4EY7

Crystal Structure of Recombinant Human Acetylcholinesterase in Complex with Donepezil


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.35 Å
  • R-Value Free: 0.211 
  • R-Value Work: 0.175 
  • R-Value Observed: 0.177 

Starting Model: experimental
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This is version 2.2 of the entry. See complete history


Literature

Structures of human acetylcholinesterase in complex with pharmacologically important ligands.

Cheung, J.Rudolph, M.J.Burshteyn, F.Cassidy, M.S.Gary, E.N.Love, J.Franklin, M.C.Height, J.J.

(2012) J Med Chem 55: 10282-10286

  • DOI: https://doi.org/10.1021/jm300871x
  • Primary Citation of Related Structures:  
    4EY4, 4EY5, 4EY6, 4EY7, 4EY8

  • PubMed Abstract: 

    Human acetylcholinesterase (AChE) is a significant target for therapeutic drugs. Here we present high resolution crystal structures of human AChE, alone and in complexes with drug ligands; donepezil, an Alzheimer's disease drug, binds differently to human AChE than it does to Torpedo AChE. These crystals of human AChE provide a more accurate platform for further drug development than previously available.


  • Organizational Affiliation

    New York Structural Biology Center, New York, New York 10027, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Acetylcholinesterase
A, B
542Homo sapiensMutation(s): 0 
Gene Names: ACHE
EC: 3.1.1.7
UniProt & NIH Common Fund Data Resources
Find proteins for P22303 (Homo sapiens)
Explore P22303 
Go to UniProtKB:  P22303
PHAROS:  P22303
GTEx:  ENSG00000087085 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP22303
Glycosylation
Glycosylation Sites: 2Go to GlyGen: P22303-1
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

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Entity ID: 2
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose
C, D
3N-Glycosylation
Glycosylation Resources
GlyTouCan:  G21290RB
GlyCosmos:  G21290RB
GlyGen:  G21290RB
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
E20
Query on E20

Download Ideal Coordinates CCD File 
E [auth A],
I [auth B]
1-BENZYL-4-[(5,6-DIMETHOXY-1-INDANON-2-YL)METHYL]PIPERIDINE
C24 H29 N O3
ADEBPBSSDYVVLD-HXUWFJFHSA-N
NAG
Query on NAG

Download Ideal Coordinates CCD File 
H [auth B]2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
EDO
Query on EDO

Download Ideal Coordinates CCD File 
F [auth A],
G [auth A],
J [auth B]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
NO3
Query on NO3

Download Ideal Coordinates CCD File 
K [auth B],
L [auth B]
NITRATE ION
N O3
NHNBFGGVMKEFGY-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.35 Å
  • R-Value Free: 0.211 
  • R-Value Work: 0.175 
  • R-Value Observed: 0.177 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 105.147α = 90
b = 105.147β = 90
c = 322.977γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
PHENIXrefinement
PDB_EXTRACTdata extraction
HKL-2000data collection
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-10-17
    Type: Initial release
  • Version 1.1: 2012-12-12
    Changes: Database references
  • Version 1.2: 2017-11-15
    Changes: Refinement description
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Derived calculations, Structure summary
  • Version 2.1: 2023-09-13
    Changes: Data collection, Database references, Refinement description, Structure summary
  • Version 2.2: 2024-11-20
    Changes: Structure summary