3BUH

BACE-1 complexed with compound 4


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.199 
  • R-Value Observed: 0.201 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Tyramine fragment binding to BACE-1

Kuglstatter, A.Stahl, M.Peters, J.U.Huber, W.Stihle, M.Schlatter, D.Benz, J.Ruf, A.Roth, D.Enderle, T.Hennig, M.

(2008) Bioorg Med Chem Lett 18: 1304-1307

  • DOI: https://doi.org/10.1016/j.bmcl.2008.01.032
  • Primary Citation of Related Structures:  
    3BRA, 3BUF, 3BUG, 3BUH

  • PubMed Abstract: 

    Fragment screening revealed that tyramine binds to the active site of the Alzheimer's disease drug target BACE-1. Hit expansion by selection of compounds from the Roche compound library identified tyramine derivatives with improved binding affinities as monitored by surface plasmon resonance. X-ray structures show that the amine of the tyramine fragment hydrogen-bonds to the catalytic water molecule. Structure-guided ligand design led to the synthesis of further low molecular weight compounds that are starting points for chemical leads.


  • Organizational Affiliation

    F. Hoffmann-La Roche, Pharma Research Basel, Grenzacherstr., 4070 Basel, Switzerland.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
beta-secretase 1409Homo sapiensMutation(s): 1 
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
AED
Query on AED

Download Ideal Coordinates CCD File 
B [auth A]4-(2-aminoethyl)-2-cyclohexylphenol
C14 H21 N O
DOCCSEDGBYCYLS-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
AED BindingDB:  3BUH Kd: 2.20e+5 (nM) from 1 assay(s)
PDBBind:  3BUH Kd: 2.20e+5 (nM) from 1 assay(s)
Binding MOAD:  3BUH Kd: 2.20e+5 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.199 
  • R-Value Observed: 0.201 
  • Space Group: P 61 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 102.491α = 90
b = 102.491β = 90
c = 170.063γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-03-11
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2021-11-10
    Changes: Database references, Derived calculations