2QK5

Structure of BACE1 bound to SCH626485


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.190 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Potent pyrrolidine- and piperidine-based BACE-1 inhibitors.

Iserloh, U.Wu, Y.Cumming, J.N.Pan, J.Wang, L.Y.Stamford, A.W.Kennedy, M.E.Kuvelkar, R.Chen, X.Parker, E.M.Strickland, C.Voigt, J.

(2008) Bioorg Med Chem Lett 18: 414-417

  • DOI: https://doi.org/10.1016/j.bmcl.2007.10.116
  • Primary Citation of Related Structures:  
    2QK5, 2QMD, 2QMF, 2QP8

  • PubMed Abstract: 

    Based on lead compound 1 identified from the patent literature, we developed novel patentable BACE-1 inhibitors by introducing a cyclic amine scaffold. Extensive SAR studies on both pyrrolidines and piperidines ultimately led to inhibitor 2f, one of the most potent inhibitors synthesized to date.


  • Organizational Affiliation

    Department of Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. ulrich.iserloh@spcorp.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-secretase 1
A, B
395Homo sapiensMutation(s): 0 
Gene Names: BACE1BACE
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
CS5
Query on CS5

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
N'-{(1S,2R)-1-(3,5-DIFLUOROBENZYL)-2-HYDROXY-3-[(3-METHOXYBENZYL)AMINO]PROPYL}-5-METHYL-N,N-DIPROPYLISOPHTHALAMIDE
C33 H41 F2 N3 O4
JEEOUWBWJFSMIP-IOWSJCHKSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
CS5 Binding MOAD:  2QK5 IC50: 8 (nM) from 1 assay(s)
BindingDB:  2QK5 IC50: min: 15, max: 80 (nM) from 4 assay(s)
PDBBind:  2QK5 IC50: 8 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.190 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 86.485α = 90
b = 89.204β = 90
c = 131.147γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
PDB_EXTRACTdata extraction
CrystalCleardata collection
HKL-2000data reduction
CNSphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-03-11
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-10-18
    Changes: Refinement description