2B8V

Crystal structure of human Beta-secretase complexed with L-L000430,469


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.358 
  • R-Value Work: 0.346 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Conformationally biased P3 amide replacements of beta-secretase inhibitors.

Stachel, S.J.Coburn, C.A.Steele, T.G.Crouthamel, M.-C.Pietrak, B.L.Lai, M.-T.Holloway, M.K.Munshi, S.K.Graham, S.L.Vacca, J.P.

(2006) Bioorg Med Chem Lett 16: 641-644

  • DOI: https://doi.org/10.1016/j.bmcl.2005.10.032
  • Primary Citation of Related Structures:  
    2B8L, 2B8V

  • PubMed Abstract: 

    We have synthesized and evaluated a series of conformationally biased P3 amide replacements based on an isophthalamide lead structure. The studies resulted in the identification of the beta-secretase inhibitor 7m which has an in vitro IC(50)=35 nM. The synthesis and biological activities of these compounds are described.


  • Organizational Affiliation

    Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. shawn_stachel@merck.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-secretase 1405Homo sapiensMutation(s): 2 
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
3BN
Query on 3BN

Download Ideal Coordinates CCD File 
B [auth A]3-BENZOYL-N-[(1S,2R)-1-BENZYL-3-(CYCLOPROPYLAMINO)-2-HYDROXYPROPYL]-5-[METHYL(METHYLSULFONYL)AMINO]BENZAMIDE
C29 H33 N3 O5 S
WCVRLSCSQDAERN-RRPNLBNLSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
3BN PDBBind:  2B8V IC50: 98 (nM) from 1 assay(s)
BindingDB:  2B8V IC50: 98 (nM) from 1 assay(s)
Binding MOAD:  2B8V IC50: 98 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.358 
  • R-Value Work: 0.346 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 104.9α = 90
b = 127.4β = 90
c = 76.4γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
SCALEPACKdata scaling
CNXrefinement
HKL-2000data reduction
CNXphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-12-06
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2021-10-20
    Changes: Database references, Derived calculations
  • Version 1.4: 2023-08-23
    Changes: Data collection, Refinement description