4M0F

Structure of human acetylcholinesterase in complex with territrem B


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.211 
  • R-Value Work: 0.175 
  • R-Value Observed: 0.177 

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Ligand Structure Quality Assessment 


This is version 2.1 of the entry. See complete history


Literature

Structures of human acetylcholinesterase bound to dihydrotanshinone I and territrem B show peripheral site flexibility.

Cheung, J.Gary, E.N.Shiomi, K.Rosenberry, T.L.

(2013) ACS Med Chem Lett 4: 1091-1096

  • DOI: https://doi.org/10.1021/ml400304w
  • Primary Citation of Related Structures:  
    4M0E, 4M0F

  • PubMed Abstract: 

    Acetylcholinesterase is a critical enzyme that regulates neurotransmission by degrading the neurotransmitter acetylcholine in synapses of the nervous system. It is an important target for both therapeutic drugs that treat Alzheimer's disease and chemical warfare agents that cripple the nervous system and cause death through paralysis. The enzyme has both catalytic and peripheral sites to which inhibitors may bind. Structures of recombinant human acetylcholinesterase in complex with the natural product inhibitors dihydrotanshinone I and territrem B reveal dihydrotanshinone I binding that is specific to only the peripheral site and territrem B binding that spans both sites and distorts the protein backbone in the peripheral site. These inhibitors may function as important molecular templates for therapeutics used for treatment of disease and protection against nerve agents.


  • Organizational Affiliation

    New York Structural Biology Center, New York, New York 10027, United States.


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
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

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
1YK
Query on 1YK

Download Ideal Coordinates CCD File 
E [auth A],
I [auth B]
territrem B
C29 H34 O9
PBXNNDFKPQPJBB-VJLHXPKFSA-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
Binding Affinity Annotations 
IDSourceBinding Affinity
1YK BindingDB:  4M0F Ki: 1.7 (nM) from 1 assay(s)
IC50: min: 6, max: 8 (nM) from 3 assay(s)
PDBBind:  4M0F Ki: 1.7 (nM) from 1 assay(s)
Binding MOAD:  4M0F Ki: 1.7 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 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 = 105.143α = 90
b = 105.143β = 90
c = 322.281γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
PHASERphasing
PHENIXrefinement
PDB_EXTRACTdata extraction
CBASSdata 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: 2013-10-16
    Type: Initial release
  • Version 1.1: 2014-04-02
    Changes: Database references
  • Version 1.2: 2014-07-16
    Changes: Database references
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Derived calculations, Structure summary
  • Version 2.1: 2023-09-20
    Changes: Data collection, Database references, Refinement description, Structure summary