3CIB

Structure of BACE Bound to SCH727596


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.72 Å
  • R-Value Free: 0.216 
  • R-Value Work: 0.188 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Rational design of novel, potent piperazinone and imidazolidinone BACE1 inhibitors

Cumming, J.N.Le, T.X.Babu, S.Carroll, C.Chen, X.Favreau, L.Gaspari, P.Guo, T.Hobbs, D.W.Huang, Y.Iserloh, U.Kennedy, M.E.Kuvelkar, R.Li, G.Lowrie, J.McHugh, N.A.Ozgur, L.Pan, J.Parker, E.M.Saionz, K.Stamford, A.W.Strickland, C.Tadesse, D.Voigt, J.Wang, L.Wu, Y.Zhang, L.Zhang, Q.

(2008) Bioorg Med Chem Lett 18: 3236-3241

  • DOI: https://doi.org/10.1016/j.bmcl.2008.04.050
  • Primary Citation of Related Structures:  
    3CIB, 3CIC, 3CID

  • PubMed Abstract: 

    Guided by structure-based design, we synthesized two novel series of potent inhibitors of BACE1 and generated extensive SAR around both the prime and non-prime side binding pockets. The key feature of both series is a cyclic amine motif specifically crafted to achieve interactions with both the flap and with the S2' pocket.


  • Organizational Affiliation

    Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. jared.cumming@spcorp.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-secretase 1
A, B
390Homo 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 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
314
Query on 314

Download Ideal Coordinates CCD File 
C [auth A],
E [auth B]
N'-[(1S,2R)-2-[(2R,4S)-4-benzylpiperidin-2-yl]-1-(3,5-difluorobenzyl)-2-hydroxyethyl]-5-methyl-N,N-dipropylbenzene-1,3-dicarboxamide
C36 H45 F2 N3 O3
UKXYKYZOSFWZIM-FLQGXGFZSA-N
TAR
Query on TAR

Download Ideal Coordinates CCD File 
D [auth A],
F [auth B]
D(-)-TARTARIC ACID
C4 H6 O6
FEWJPZIEWOKRBE-LWMBPPNESA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
314 Binding MOAD:  3CIB IC50: 14 (nM) from 1 assay(s)
PDBBind:  3CIB IC50: 14 (nM) from 1 assay(s)
BindingDB:  3CIB IC50: min: 14, max: 522 (nM) from 2 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.72 Å
  • R-Value Free: 0.216 
  • R-Value Work: 0.188 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 86.677α = 90
b = 89.435β = 90
c = 131.446γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
PDB_EXTRACTdata extraction
ADSCdata collection
CNSphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-06-10
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-10-25
    Changes: Refinement description