2VJ7

Human BACE-1 in complex with 3-(ethylamino)-N-((1S,2R)-2-hydroxy-1-(phenylmethyl)-3-(((3-(trifluoromethyl)phenyl)methyl)amino)propyl)-5-(2-oxo-1-pyrrolidinyl)benzamide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.231 
  • R-Value Work: 0.209 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Bace-1 Inhibitors Part 2: Identification of Hydroxy Ethylamines (Heas) with Reduced Peptidic Character.

Clarke, B.Demont, E.Dingwall, C.Dunsdon, R.Faller, A.Hawkins, J.Hussain, I.Macpherson, D.Maile, G.Matico, R.Milner, P.Mosley, J.Naylor, A.O'Brien, A.Redshaw, S.Riddell, D.Rowland, P.Soleil, V.Smith, K.Stanway, S.Stemp, G.Sweitzer, S.Theobald, P.Vesey, D.Walter, D.S.Ward, J.Wayne, G.

(2008) Bioorg Med Chem Lett 18: 1017

  • DOI: https://doi.org/10.1016/j.bmcl.2007.12.019
  • Primary Citation of Related Structures:  
    2VIE, 2VJ6, 2VJ7, 2VJ9

  • PubMed Abstract: 

    This paper describes the discovery of non-peptidic, potent, and selective hydroxy ethylamine (HEA) inhibitors of BACE-1 by replacement of the prime side of a lead di-amide 2. Inhibitors with nanosmolar potency and high selectivity were identified. Depending on the nature of the P(1)(') and P(2)(') substituents, two different binding modes were observed in X-ray co-crystal structures.


  • Organizational Affiliation

    Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, United Kingdom.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
BETA-SECRETASE 1392Homo sapiensMutation(s): 4 
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
VG6
Query on VG6

Download Ideal Coordinates CCD File 
B [auth A]N-[(1S,2R)-1-benzyl-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propyl]-3-(ethylamino)-5-(2-oxopyrrolidin-1-yl)benzamide
C31 H35 F3 N4 O3
QPGDTFHILHXFBQ-WUFINQPMSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
VG6 BindingDB:  2VJ7 IC50: min: 40, max: 200 (nM) from 4 assay(s)
Binding MOAD:  2VJ7 IC50: 40 (nM) from 1 assay(s)
PDBBind:  2VJ7 IC50: 40 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.231 
  • R-Value Work: 0.209 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 48.335α = 90
b = 77.214β = 90
c = 103.928γ = 90
Software Package:
Software NamePurpose
CNXrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2008-01-29
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2019-03-06
    Changes: Data collection, Experimental preparation, Other
  • Version 1.4: 2019-05-15
    Changes: Data collection, Experimental preparation