2VIZ

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


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.227 
  • R-Value Work: 0.198 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Bace-1 Inhibitors Part 1: Identification of Novel Hydroxy Ethylamines (Heas).

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: 1011

  • DOI: https://doi.org/10.1016/j.bmcl.2007.12.017
  • Primary Citation of Related Structures:  
    2VIY, 2VIZ

  • PubMed Abstract: 

    Inhibition of the aspartyl protease BACE-1 has the potential to deliver a disease-modifying therapy for Alzheimer's disease. Herein, is described the lead generation effort which resulted, with the support of X-ray crystallography, in the discovery of potent inhibitors based on a hydroxy ethylamine (HEA) transition-state mimetic. These inhibitors were capable of lowering amyloid production in a cell-based assay.


  • 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
VG4
Query on VG4

Download Ideal Coordinates CCD File 
B [auth A]N-[(1S,2R)-1-benzyl-3-{[(1S)-2-(cyclohexylamino)-1-methyl-2-oxoethyl]amino}-2-hydroxypropyl]-3-(2-oxo-2,3-dihydro-1H-pyrrol-1-yl)-5-propoxybenzamide
C33 H44 N4 O5
OCMGZBXBWVXWRJ-KEPSJGTLSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
VG4 PDBBind:  2VIZ IC50: 605 (nM) from 1 assay(s)
Binding MOAD:  2VIZ IC50: 605 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.227 
  • R-Value Work: 0.198 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 48.744α = 90
b = 76.969β = 90
c = 104.219γ = 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