RCSB PDB - 2QP8: Structure of BACE Bound to SCH734723

 2QP8

Structure of BACE Bound to SCH734723


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.206 
  • R-Value Work: 0.188 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted SC7Click on this verticalbar to view details

This is version 1.3 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
Binding Affinity Annotations 
IDSourceBinding Affinity
SC7 PDBBind:  2QP8 IC50: 8 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.50 Å
  • R-Value Free: 0.206 
  • R-Value Work: 0.188 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 86.447α = 90
b = 89.08β = 90
c = 131.033γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
PDB_EXTRACTdata extraction
MAR345data collection
HKL-2000data reduction
HKL-2000data scaling
CNSphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted SC7Click on this verticalbar to view details

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: 2017-10-25
    Changes: Refinement description
  • Version 1.3: 2024-11-20
    Changes: Data collection, Database references, Derived calculations, Structure summary