3LPI

Structure of BACE Bound to SCH745132


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.05 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.202 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Piperazine sulfonamide BACE1 inhibitors: design, synthesis, and in vivo characterization.

Cumming, J.Babu, S.Huang, Y.Carrol, C.Chen, X.Favreau, L.Greenlee, W.Guo, T.Kennedy, M.Kuvelkar, R.Le, T.Li, G.McHugh, N.Orth, P.Ozgur, L.Parker, E.Saionz, K.Stamford, A.Strickland, C.Tadesse, D.Voigt, J.Zhang, L.Zhang, Q.

(2010) Bioorg Med Chem Lett 20: 2837-2842

  • DOI: https://doi.org/10.1016/j.bmcl.2010.03.050
  • Primary Citation of Related Structures:  
    3LNK, 3LPI, 3LPJ, 3LPK

  • PubMed Abstract: 

    With collaboration between chemistry, X-ray crystallography, and molecular modeling, we designed and synthesized a series of novel piperazine sulfonamide BACE1 inhibitors. Iterative exploration of the non-prime side and S2' sub-pocket of the enzyme culminated in identification of an analog that potently lowers peripheral Abeta(40) in transgenic mice with a single subcutaneous dose.


  • Organizational Affiliation

    Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. jared.cumming@merck.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-secretase 1
A, B
455Homo sapiensMutation(s): 0 
Gene Names: BACEBACE1KIAA1149
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
Z74
Query on Z74

Download Ideal Coordinates CCD File 
D [auth A],
F [auth B]
N'-{(1S,2S)-1-(3,5-difluorobenzyl)-2-hydroxy-2-[(2R)-4-(phenylsulfonyl)piperazin-2-yl]ethyl}-5-methyl-N,N-dipropylbenzene-1,3-dicarboxamide
C34 H42 F2 N4 O5 S
KDRUCCZCGHVXGH-QAXCHELISA-N
TLA
Query on TLA

Download Ideal Coordinates CCD File 
C [auth A],
E [auth B]
L(+)-TARTARIC ACID
C4 H6 O6
FEWJPZIEWOKRBE-JCYAYHJZSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
Z74 BindingDB:  3LPI Ki: 3 (nM) from 1 assay(s)
IC50: 120 (nM) from 1 assay(s)
Binding MOAD:  3LPI Ki: 3 (nM) from 1 assay(s)
PDBBind:  3LPI Ki: 3 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.05 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.202 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 86.427α = 90
b = 89.451β = 90
c = 131.355γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
PDB_EXTRACTdata extraction
ADSCdata collection
HKL-2000data reduction
HKL-2000data scaling
CNXphasing
CNXrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-04-14
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-11-01
    Changes: Refinement description