3SKG

Crystal structure of beta-site app-cleaving enzyme 1 (BACE-WT) complex with (2S)-2-((3R)-3-acetamido-3-isobutyl-2-oxo-1-pyrrolidinyl)-N-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-2-(1,2,3,4-tetrahydro-3-isoquinolinyl)ethyl)-4-phenylbutanamide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.88 Å
  • R-Value Free: 0.348 
  • R-Value Work: 0.255 
  • R-Value Observed: 0.259 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Synthesis and in vivo evaluation of cyclic diaminopropane BACE-1 inhibitors.

Thompson, L.A.Shi, J.Decicco, C.P.Tebben, A.J.Olson, R.E.Boy, K.M.Guernon, J.M.Good, A.C.Liauw, A.Zheng, C.Copeland, R.A.Combs, A.P.Trainor, G.L.Camac, D.M.Muckelbauer, J.K.Lentz, K.A.Grace, J.E.Burton, C.R.Toyn, J.H.Barten, D.M.Marcinkeviciene, J.Meredith, J.E.Albright, C.F.Macor, J.E.

(2011) Bioorg Med Chem Lett 21: 6909-6915

  • DOI: https://doi.org/10.1016/j.bmcl.2011.06.116
  • Primary Citation of Related Structures:  
    3SKF, 3SKG

  • PubMed Abstract: 

    The synthesis, evaluation, and structure-activity relationships of a set of related constrained diaminopropane inhibitors of BACE-1 are described. The full in vivo profile of an optimized inhibitor in both normal and P-gp deficient mice is compared with data generated in normal rats.


  • Organizational Affiliation

    Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA. lorin.thompson@bms.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-secretase 1A,
B,
C [auth D],
D [auth E]
455Homo sapiensMutation(s): 0 
Gene Names: BACE1BACEKIAA1149
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
PB8
Query on PB8

Download Ideal Coordinates CCD File 
E [auth A],
F [auth B],
G [auth D],
H [auth E]
(2S)-2-[(3R)-3-(acetylamino)-3-(2-methylpropyl)-2-oxopyrrolidin-1-yl]-N-{(1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-[(3R)-1,2,3,4-tetrahydroisoquinolin-3-yl]propan-2-yl}-4-phenylbutanamide
C38 H46 F2 N4 O4
JJJDOYFRIVNWHV-WUCUQKTKSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
PB8 PDBBind:  3SKG IC50: 8 (nM) from 1 assay(s)
BindingDB:  3SKG IC50: min: 8.6, max: 9.5 (nM) from 2 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.88 Å
  • R-Value Free: 0.348 
  • R-Value Work: 0.255 
  • R-Value Observed: 0.259 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 86.24α = 90
b = 130.451β = 96.65
c = 86.872γ = 90
Software Package:
Software NamePurpose
SCALEPACKdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
CrystalCleardata collection
HKL-2000data reduction
HKL-2000data scaling
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: 2011-09-07
    Type: Initial release
  • Version 1.1: 2011-10-19
    Changes: Database references
  • Version 1.2: 2011-11-02
    Changes: Database references
  • Version 1.3: 2012-12-05
    Changes: Database references