4BEK

CRYSTAL STRUCTURE OF BACE-1 IN COMPLEX WITH CHEMICAL LIGAND


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.39 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.205 
  • R-Value Observed: 0.207 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Bace1 Inhibitors: A Head Group Scan on a Series of Amides.

Woltering, T.J.Wostl, W.Hilpert, H.Rogers-Evans, M.Pinard, E.Mayweg, A.Gobel, M.Banner, D.W.Benz, J.Travagli, M.Pollastrini, M.Marconi, G.Gabellieri, E.Guba, W.Mauser, H.Andreini, M.Jacobsen, H.Power, E.Narquizian, R.

(2013) Bioorg Med Chem Lett 23: 4239

  • DOI: https://doi.org/10.1016/j.bmcl.2013.05.003
  • Primary Citation of Related Structures:  
    4BEK, 4BFD

  • PubMed Abstract: 

    A series of amides bearing a variety of amidine head groups was investigated as BACE1 inhibitors with respect to inhibitory activity in a BACE1 enzyme as well as a cell-based assay. Determination of their basicity as well as their properties as substrates of P-glycoprotein revealed that a 2-amino-1,3-oxazine head group would be a suitable starting point for further development of brain penetrating compounds for potential Alzheimer's disease treatment.


  • Organizational Affiliation

    F. Hoffmann-La Roche Ltd., Pharma Research, Grenzacherstr. 124, CH-4070 Basel, Switzerland. thomas.woltering@roche.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
BETA-SECRETASE 1409Homo sapiensMutation(s): 1 
EC: 3.4.23.46
UniProt & NIH Common Fund Data Resources
Find proteins for P56817 (Homo sapiens)
Explore P56817 
Go to UniProtKB:  P56817
PHAROS:  P56817
GTEx:  ENSG00000186318 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP56817
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
XK0 PDBBind:  4BEK IC50: 4.12e+4 (nM) from 1 assay(s)
BindingDB:  4BEK IC50: 4.12e+4 (nM) from 1 assay(s)
Binding MOAD:  4BEK IC50: 4.12e+4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.39 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.205 
  • R-Value Observed: 0.207 
  • Space Group: P 61 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 103.592α = 90
b = 103.592β = 90
c = 166.71γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
SADABSdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-06-19
    Type: Initial release
  • Version 1.1: 2013-07-10
    Changes: Database references
  • Version 1.2: 2019-01-30
    Changes: Data collection, Experimental preparation
  • Version 1.3: 2019-02-06
    Changes: Data collection, Experimental preparation
  • Version 1.4: 2023-12-20
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description