2QZL

Crystal Structure of human Beta Secretase complexed with IXS


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.241 
  • R-Value Work: 0.216 
  • R-Value Observed: 0.217 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

BACE-1 inhibition by a series of psi[CH2NH] reduced amide isosteres

Coburn, C.A.Stachel, S.J.Jones, K.G.Steele, T.G.Rush, D.M.DiMuzio, J.Pietrak, B.L.Lai, M.T.Huang, Q.Lineberger, J.Jin, L.Munshi, S.Holloway, K.M.Espeseth, A.Simon, A.Hazuda, D.Graham, S.L.Vacca, J.P.

(2006) Bioorg Med Chem Lett 16: 3635-3638

  • DOI: https://doi.org/10.1016/j.bmcl.2006.04.076
  • Primary Citation of Related Structures:  
    2QZL

  • PubMed Abstract: 

    A series of beta-site amyloid precursor protein cleaving enzyme (BACE-1) inhibitors containing a psi(CH2NH) reduced amide bond were synthesized. Incorporation of this reduced amide isostere as a non-cleavable peptide surrogate afforded inhibitors possessing low nanomolar potencies in both an enzymatic and cell-based assay.


  • Organizational Affiliation

    Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 4, West Point, PA 19486, USA. craig_coburn@merck.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-secretase 1411Homo 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
IXS
Query on IXS

Download Ideal Coordinates CCD File 
B [auth A]N-[(1S)-1-benzyl-2-{[(1S)-2-(isobutylamino)-1-methyl-2-oxoethyl]amino}ethyl]-N'-[(1R)-1-(4-fluorophenyl)ethyl]-5-[methyl(methylsulfonyl)amino]isophthalamide
C34 H44 F N5 O5 S
FZTXBRKPIRTQCY-QEGDFHJFSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
IXS Binding MOAD:  2QZL IC50: 8 (nM) from 1 assay(s)
BindingDB:  2QZL IC50: 8 (nM) from 1 assay(s)
PDBBind:  2QZL IC50: 8 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.241 
  • R-Value Work: 0.216 
  • R-Value Observed: 0.217 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 104.931α = 90
b = 128.152β = 90
c = 76.307γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
d*TREKdata reduction
d*TREKdata scaling
REFMACphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

  • Released Date: 2008-04-22 
  • Deposition Author(s): Munshi, S.

Revision History  (Full details and data files)

  • Version 1.0: 2008-04-22
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2021-10-20
    Changes: Database references, Derived calculations
  • Version 1.3: 2023-08-30
    Changes: Data collection, Refinement description