2B8L

Crystal structure of human beta secretase complexed with inhibitor

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.252 
  • R-Value Work: 0.220 
  • R-Value Observed: 0.230 

Starting Model: experimental
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wwPDB Validation   3D Report Full Report


This is version 1.5 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. [email protected]


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-secretase 1405Homo sapiensMutation(s): 2 
Gene Names: BACE1, BACE
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
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
5HA
Query on 5HA
Download Ideal Coordinates CCD File 
B [auth A]N-[(1S,2R)-1-BENZYL-3-(CYCLOPROPYLAMINO)-2-HYDROXYPROPYL]-5-[METHYL(METHYLSULFONYL)AMINO]-N'-[(1R)-1-PHENYLETHYL]ISOPHTHALAMIDE
C31 H38 N4 O5 S
VPNIQGRFZCTBEZ-SPTGULJVSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
5HA BindingDB:  2B8L Ki: 233 (nM) from 1 assay(s)
IC50: min: 10, max: 1.50e+4 (nM) from 13 assay(s)
EC50: 43 (nM) from 1 assay(s)
PDBBind:  2B8L IC50: 15 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.252 
  • R-Value Work: 0.220 
  • R-Value Observed: 0.230 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 104.678α = 90
b = 127.917β = 90
c = 76.122γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
SCALEPACKdata scaling
CNXrefinement
HKL-2000data reduction
CNXphasing

Structure Validation

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View more in-depth experimental data
Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-10-18
    Type: Initial release
  • Version 1.1: 2007-10-11
    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
  • Version 1.5: 2024-10-30
    Changes: Structure summary