6QAA

Human Butyrylcholinesterase in complex with (S)-2-(butylamino)-N-(2-cycloheptylethyl)-3-(1H-indol-3-yl)propanamide

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.208 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.178 

Starting Model: experimental
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wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 2.2 of the entry. See complete history. 


Literature

Tryptophan-derived butyrylcholinesterase inhibitors as promising leads against Alzheimer's disease.

Meden, A., Knez, D., Jukic, M., Brazzolotto, X., Grsic, M., Pislar, A., Zahirovic, A., Kos, J., Nachon, F., Svete, J., Gobec, S., Groselj, U.

(2019) Chem Commun (Camb) 55: 3765-3768

  • DOI: https://doi.org/10.1039/c9cc01330j
  • Primary Citation of Related Structures:  
    6QAA, 6QAB, 6QAC, 6QAD, 6QAE

  • PubMed Abstract: 

    We have identified tryptophan-based selective nanomolar butyrylcholinesterase (BChE) inhibitors. They are defined according to their chemical modularity, novel binding mode revealed by five solved crystal structures with human BChE, low cytotoxicity, and predicted permeability of the blood-brain barrier. Altogether, these factors indicate their potential as unique lead compounds for symptomatic therapy against Alzheimer's disease.

    • Organizational Affiliation: 

    Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia. [email protected].


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Cholinesterase557Homo sapiensMutation(s): 4 
Gene Names: BCHE, CHE1
EC: 3.1.1.8
UniProt & NIH Common Fund Data Resources
Find proteins for P06276 (Homo sapiens)
Explore P06276 
Go to UniProtKB:  P06276
PHAROS:  P06276
GTEx:  ENSG00000114200 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP06276
Glycosylation
Glycosylation Sites: 6
Go to GlyGen: P06276-1
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 2
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose
B
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G86851RC
GlyCosmos:  G86851RC
GlyGen:  G86851RC
Entity ID: 3
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 6 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
HUN (Subject of Investigation/LOI)
Query on HUN
Download Ideal Coordinates CCD File 
I [auth A]butyl-[(2~{S})-1-(2-cycloheptylethylamino)-3-(1~{H}-indol-3-yl)-1-oxidanylidene-propan-2-yl]azanium
C24 H38 N3 O
LDOSYPMIOHKIEJ-QHCPKHFHSA-O
NAG
Query on NAG
Download Ideal Coordinates CCD File 
E [auth A],
F [auth A],
G [auth A]		2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
MES
Query on MES
Download Ideal Coordinates CCD File 
O [auth A]2-(N-MORPHOLINO)-ETHANESULFONIC ACID
C6 H13 N O4 S
SXGZJKUKBWWHRA-UHFFFAOYSA-N
SO4
Query on SO4
Download Ideal Coordinates CCD File 
P [auth A],
Q [auth A],
R [auth A],
S [auth A]		SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
GOL
Query on GOL
Download Ideal Coordinates CCD File 
J [auth A],
K [auth A],
L [auth A],
M [auth A]		GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
DMS
Query on DMS
Download Ideal Coordinates CCD File 
H [auth A],
N [auth A]		DIMETHYL SULFOXIDE
C2 H6 O S
IAZDPXIOMUYVGZ-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.208 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.178 
  • Space Group: I 4 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 154.597α = 90
b = 154.597β = 90
c = 128.214γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
Cootmodel building
XDSdata reduction
XDSdata scaling
PHENIXphasing

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History & Funding Information

Deposition Data

Funding OrganizationLocationGrant Number
French Ministry of Armed ForcesFrancePDH-2-NRBC-3-C-3201

Revision History  (Full details and data files)

  • Version 1.0: 2019-03-27
    Type: Initial release
  • Version 1.1: 2019-04-03
    Changes: Data collection, Database references
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Derived calculations, Structure summary
  • Version 2.1: 2024-01-24
    Changes: Data collection, Database references, Derived calculations, Refinement description, Structure summary
  • Version 2.2: 2024-11-06
    Changes: Structure summary