3IXJ

Crystal structure of beta-secretase 1 in complex with selective beta-secretase 1 inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.243 
  • R-Value Work: 0.212 
  • R-Value Observed: 0.213 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Design and Synthesis of Potent and Selective BACE-1 Inhibitors.

Bjorklund, C.Oscarson, S.Benkestock, K.Borkakoti, N.Jansson, K.Lindberg, J.Vrang, L.Hallberg, A.Rosenquist, A.Samuelsson, B.

(2010) J Med Chem 53: 1458-1464

  • DOI: https://doi.org/10.1021/jm901168f
  • Primary Citation of Related Structures:  
    3IXJ

  • PubMed Abstract: 

    Highly potent BACE-1 protease inhibitors have been developed from an inhibitors containing a hydroxyethylene (HE) core displaying aryloxymethyl or benzyloxymethyl P1 side chain and a methoxy P1' side chain. The target molecules were synthesized in good overall yields from chiral carbohydrate starting materials. The inhibitors show high BACE-1 potency and good selectivity against cathepsin D, where the most potent inhibitor furnishes BACE-1 K(i) << 1 nM and displays >1000-fold selectivity over cathepsin D.


  • Organizational Affiliation

    Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-secretase 1
A, B, C
388Homo 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
Binding Affinity Annotations 
IDSourceBinding Affinity
586 BindingDB:  3IXJ Ki: 1 (nM) from 1 assay(s)
IC50: 0.32 (nM) from 1 assay(s)
Binding MOAD:  3IXJ IC50: 0.32 (nM) from 1 assay(s)
PDBBind:  3IXJ IC50: 0.32 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.243 
  • R-Value Work: 0.212 
  • R-Value Observed: 0.213 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 81.913α = 90
b = 102.705β = 103.42
c = 100.417γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-03-02
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance