3EXO

Crystal structure of BACE1 bound to inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.295 
  • R-Value Work: 0.229 
  • R-Value Observed: 0.232 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Identification of a small molecule beta-secretase inhibitor that binds without catalytic aspartate engagement.

Steele, T.G.Hills, I.D.Nomland, A.A.de Leon, P.Allison, T.McGaughey, G.Colussi, D.Tugusheva, K.Haugabook, S.J.Espeseth, A.S.Zuck, P.Graham, S.L.Stachel, S.J.

(2009) Bioorg Med Chem Lett 19: 17-20

  • DOI: https://doi.org/10.1016/j.bmcl.2008.11.027
  • Primary Citation of Related Structures:  
    3EXO

  • PubMed Abstract: 

    A small molecule inhibitor of beta-secretase with a unique binding mode has been developed. Crystallographic determination of the enzyme-inhibitor complex shows the catalytic aspartate residues in the active site are not engaged in inhibitor binding. This unprecedented binding mode in the field of aspartyl protease inhibition is described.


  • Organizational Affiliation

    Department of Medicinal Chemistry, Merck Research Laboratories, Merck & Co, West Point, PA 19486, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-secretase 1413Homo sapiensMutation(s): 2 
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
Binding Affinity Annotations 
IDSourceBinding Affinity
5MS BindingDB:  3EXO IC50: 2.40e+4 (nM) from 1 assay(s)
PDBBind:  3EXO IC50: 2.40e+4 (nM) from 1 assay(s)
Binding MOAD:  3EXO IC50: 2.40e+4 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.295 
  • R-Value Work: 0.229 
  • R-Value Observed: 0.232 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 104.433α = 90
b = 127.923β = 90
c = 76.671γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
StructureStudiodata collection
MOLREPphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-02-03
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.2: 2017-10-25
    Changes: Refinement description
  • Version 1.3: 2021-10-20
    Changes: Database references, Derived calculations
  • Version 1.4: 2023-12-27
    Changes: Data collection