3NSH

BACE-1 in complex with ELN475957


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.279 
  • R-Value Work: 0.231 
  • R-Value Observed: 0.233 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Design and synthesis of hydroxyethylamine (HEA) BACE-1 inhibitors: structure-activity relationship of the aryl region.

Probst, G.D.Bowers, S.Sealy, J.M.Stupi, B.Dressen, D.Jagodzinska, B.M.Aquino, J.Gailunas, A.Truong, A.P.Tso, L.Xu, Y.Z.Hom, R.K.John, V.Tung, J.S.Pleiss, M.A.Tucker, J.A.Konradi, A.W.Sham, H.L.Jagodzinski, J.Toth, G.Brecht, E.Yao, N.Pan, H.Lin, M.Artis, D.R.Ruslim, L.Bova, M.P.Sinha, S.Yednock, T.A.Gauby, S.Zmolek, W.Quinn, K.P.Sauer, J.M.

(2010) Bioorg Med Chem Lett 20: 6034-6039

  • DOI: https://doi.org/10.1016/j.bmcl.2010.08.070
  • Primary Citation of Related Structures:  
    3NSH

  • PubMed Abstract: 

    The structure-activity relationship of the prime region of hydroxyethylamine BACE inhibitors is described. Variation in the aryl linker region with 5- and 6-membered heterocycles provided compounds such as 33 with improved permeability and reduced P-gp liability compared to benzyl amine analog 1.


  • Organizational Affiliation

    Department of Medicinal Chemistry, Elan Pharmaceuticals, South San Francisco, CA 94080, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-secretase 1
A, B, C
406Homo sapiensMutation(s): 0 
Gene Names: BACE1BACEKIAA1149
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 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
957
Query on 957

Download Ideal Coordinates CCD File 
D [auth A],
E [auth B],
F [auth C]
N-[(1S,2R)-1-(3,5-difluorobenzyl)-3-({1-[4-(2,2-dimethylpropyl)thiophen-2-yl]cyclopropyl}amino)-2-hydroxypropyl]acetamide
C24 H32 F2 N2 O2 S
YEGCCSKZPHGALE-LEWJYISDSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
957 BindingDB:  3NSH IC50: 470 (nM) from 1 assay(s)
Binding MOAD:  3NSH IC50: 470 (nM) from 1 assay(s)
PDBBind:  3NSH IC50: 470 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.279 
  • R-Value Work: 0.231 
  • R-Value Observed: 0.233 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 82.155α = 90
b = 104.592β = 104.5
c = 100.155γ = 90
Software Package:
Software NamePurpose
CrystalCleardata collection
MOLREPphasing
REFMACrefinement
d*TREKdata reduction
d*TREKdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-09-22
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-12-27
    Changes: Data collection, Database references, Derived calculations