3CKP

Crystal structure of BACE-1 in complex with inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.304 
  • R-Value Work: 0.245 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Synthesis, SAR, and X-ray structure of human BACE-1 inhibitors with cyclic urea derivatives

Park, H.Min, K.Kwak, H.-S.Koo, K.D.Lim, D.Seo, S.-W.Choi, J.-U.Platt, B.Choi, D.-Y.

(2008) Bioorg Med Chem Lett 18: 2900-2904

  • DOI: https://doi.org/10.1016/j.bmcl.2008.03.081
  • Primary Citation of Related Structures:  
    3CKP, 3CKR

  • PubMed Abstract: 

    We describe synthesis and evaluation of a series of cyclic urea derivatives with hydroxylethylamine isostere. Modification of P3, P1, and P2' and combination of SAR display a >100-fold increase in potency with good cellular activity (IC(50)=0.15microM) relative to the previously reported compound 3.


  • Organizational Affiliation

    Drug Discovery, Research & Development, LG Life Sciences, 104-1 Munji-dong, Yuseong-gu, Daejon 305-380, Republic of Korea. renivie@lgls.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-secretase 1
A, B, C
412Homo sapiensMutation(s): 2 
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
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
012
Query on 012

Download Ideal Coordinates CCD File 
I [auth A],
L [auth B],
O [auth C]
(4S)-N-[(1S,2R)-1-benzyl-3-{[3-(dimethylamino)benzyl]amino}-2-hydroxypropyl]-1-(3-methoxybenzyl)-2-oxoimidazolidine-4-carboxamide
C31 H39 N5 O4
MCBWJRZWLSXSBN-YTCPBCGMSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
D [auth A]
E [auth A]
F [auth A]
G [auth A]
H [auth A]
D [auth A],
E [auth A],
F [auth A],
G [auth A],
H [auth A],
J [auth B],
K [auth B],
M [auth C],
N [auth C]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Binding Affinity Annotations 
IDSourceBinding Affinity
012 Binding MOAD:  3CKP Ki: 449 (nM) from 1 assay(s)
BindingDB:  3CKP Ki: 449 (nM) from 1 assay(s)
IC50: 1.42e+4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.304 
  • R-Value Work: 0.245 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 224.064α = 90
b = 105.654β = 101.47
c = 63.7γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing
CNSrefinement
PDB_EXTRACTdata extraction
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2008-06-03 
  • Deposition Author(s): Min, K.

Revision History  (Full details and data files)

  • Version 1.0: 2008-06-03
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-10-25
    Changes: Refinement description
  • Version 1.3: 2021-11-10
    Changes: Database references, Derived calculations