5FUM

Mus musculus acetylcholinesterase in complex with AL200


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.227 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.197 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 2.0 of the entry. See complete history


Literature

Discovery of Selective Inhibitors Targeting Acetylcholinesterase 1 from Disease-Transmitting Mosquitoes.

Engdahl, C.Knutsson, S.Ekstrom, F.J.Linusson, A.

(2016) J Med Chem 17: 2724

  • DOI: https://doi.org/10.1021/acs.jmedchem.6b00967
  • Primary Citation of Related Structures:  
    5FUM

  • PubMed Abstract: 

    Vector control of disease-transmitting mosquitoes is increasingly important due to the re-emergence and spread of infections such as malaria and dengue. We have conducted a high throughput screen (HTS) of 17,500 compounds for inhibition of the essential AChE1 enzymes from the mosquitoes Anopheles gambiae and Aedes aegypti. In a differential HTS analysis including the human AChE, several structurally diverse, potent, and selective noncovalent AChE1 inhibitors were discovered. For example, a phenoxyacetamide-based inhibitor was identified with a 100-fold selectivity for the mosquito over the human enzyme. The compound also inhibited a resistance conferring mutant of AChE1. Structure-selectivity relationships could be proposed based on the enzymes' 3D structures; the hits' selectivity profiles appear to be linked to differences in two loops that affect the structure of the entire active site. Noncovalent inhibitors of AChE1, such as the ones presented here, provide valuable starting points toward insecticides and are complementary to existing and new covalent inhibitors.


  • Organizational Affiliation

    Department of Chemistry, Umeå University , SE-901 87 Umeå, Sweden.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
ACETYLCHOLINESTERASE
A, B
548Mus musculusMutation(s): 0 
EC: 3.1.1.7
UniProt & NIH Common Fund Data Resources
Find proteins for P21836 (Mus musculus)
Explore P21836 
Go to UniProtKB:  P21836
IMPC:  MGI:87876
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP21836
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SOF
Query on SOF

Download Ideal Coordinates CCD File 
C [auth A],
F [auth B]
2-(biphenyl-4-yloxy)-1-[4-(4-ethylpiperazin-1-yl)piperidin-1-yl]ethanone
C25 H33 N3 O2
BODMOCLWYAYDCG-UHFFFAOYSA-N
PE4
Query on PE4

Download Ideal Coordinates CCD File 
J [auth B]2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL
C16 H34 O8
PJWQOENWHPEPKI-UHFFFAOYSA-N
PG0
Query on PG0

Download Ideal Coordinates CCD File 
D [auth A],
E [auth A],
G [auth B],
H [auth B],
I [auth B]
2-(2-METHOXYETHOXY)ETHANOL
C5 H12 O3
SBASXUCJHJRPEV-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
SOF BindingDB:  5FUM IC50: min: 1.80e+4, max: 3.10e+4 (nM) from 2 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.227 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.197 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 78.66α = 90
b = 110.757β = 90
c = 227.571γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata 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: 2016-09-21
    Type: Initial release
  • Version 1.1: 2016-12-21
    Changes: Database references
  • Version 2.0: 2018-01-17
    Changes: Atomic model, Data collection