3LHG

Bace1 in complex with the aminohydantoin Compound 4g


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.184 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Pyridinyl aminohydantoins as small molecule BACE1 inhibitors.

Zhou, P.Li, Y.Fan, Y.Wang, Z.Chopra, R.Olland, A.Hu, Y.Magolda, R.L.Pangalos, M.Reinhart, P.H.Turner, M.J.Bard, J.Malamas, M.S.Robichaud, A.J.

(2010) Bioorg Med Chem Lett 20: 2326-2329

  • DOI: https://doi.org/10.1016/j.bmcl.2010.01.136
  • Primary Citation of Related Structures:  
    3LHG

  • PubMed Abstract: 

    A novel class of pyridinyl aminohydantoins was designed and prepared as highly potent BACE1 inhibitors. Compound (S)-4g showed excellent potency with IC(50) of 20 nM for BACE1. X-ray crystallography indicated that the interaction between pyridine nitrogen and the tryptophan Trp76 was a key feature in the S2' region of the enzyme that contributed to increased potency.


  • Organizational Affiliation

    Department of Chemical Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543-8000, United States. zhoupb31@gmail.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-secretase 1415Homo sapiensMutation(s): 0 
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
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
Z81
Query on Z81

Download Ideal Coordinates CCD File 
B [auth A](5S)-2-amino-5-(2',5'-difluorobiphenyl-3-yl)-3-methyl-5-pyridin-4-yl-3,5-dihydro-4H-imidazol-4-one
C21 H16 F2 N4 O
RKYFABJLGJZOBA-OAQYLSRUSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
Z81 BindingDB:  3LHG IC50: min: 20, max: 50 (nM) from 2 assay(s)
Binding MOAD:  3LHG IC50: 20 (nM) from 1 assay(s)
PDBBind:  3LHG IC50: 20 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.184 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 72.909α = 90
b = 104.632β = 94.89
c = 50.26γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
AMoREphasing
PHENIXrefinement
HKL-2000data reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

  • Released Date: 2010-04-21 
  • Deposition Author(s): Olland, A.M.

Revision History  (Full details and data files)

  • Version 1.0: 2010-04-21
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description