2XFK

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


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.195 
  • R-Value Work: 0.163 
  • R-Value Observed: 0.165 

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 Using Novel Edge-to-Face Interaction with Arg-296

Clarke, B.Cutler, L.Demont, E.Dingwall, C.Dunsdon, R.Hawkins, J.Howes, C.Hussain, I.Maile, G.Matico, R.Mosley, J.Naylor, A.O'Brien, A.Redshaw, S.Rowland, P.Soleil, V.Smith, K.J.Sweitzer, S.Theobald, P.Vesey, D.Walter, D.S.Wayne, G.

(2010) Bioorg Med Chem Lett 20: 4639

  • DOI: https://doi.org/10.1016/j.bmcl.2010.05.111
  • Primary Citation of Related Structures:  
    2XFI, 2XFJ, 2XFK

  • 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 a series of potent inhibitors based on an hydroxyethylamine (HEA) transition state mimetic template. These inhibitors interact with the non prime side of the enzyme using a novel edge-to-face interaction with Arg-296.


  • Organizational Affiliation

    Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D, New Frontiers Science Park, Harlow, Essex, UK.


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
AA9
Query on AA9

Download Ideal Coordinates CCD File 
B [auth A]N-((1S,2R)-3-(((1S)-2-(CYCLOHEXYLAMINO)-1--METHYL-2-OXOETHYL)AMINO)-2-HYDROXY-1-(PHENYLMETHYL)PROPYL)-3-(ETHYLAMINO)-5-((METHYLSULFONYL)(PHENYL)AMINO)BENZAMIDE
C35 H47 N5 O5 S
SMMANAWVXZZNER-DZMJNENTSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
AA9 Binding MOAD:  2XFK IC50: 3 (nM) from 1 assay(s)
BindingDB:  2XFK IC50: min: 3, max: 53 (nM) from 3 assay(s)
PDBBind:  2XFK IC50: 3 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.195 
  • R-Value Work: 0.163 
  • R-Value Observed: 0.165 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 47.864α = 90
b = 76.845β = 90
c = 104.467γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
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: 2010-07-07
    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