3DV1

Crystal structure of human beta-secretase in complex with NVP-ARV999


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.241 
  • R-Value Work: 0.207 
  • R-Value Observed: 0.223 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Macrocyclic peptidomimetic beta-secretase (BACE-1) inhibitors with activity in vivo.

Machauer, R.Laumen, K.Veenstra, S.Rondeau, J.M.Tintelnot-Blomley, M.Betschart, C.Jaton, A.L.Desrayaud, S.Staufenbiel, M.Rabe, S.Paganetti, P.Neumann, U.

(2009) Bioorg Med Chem Lett 19: 1366-1370

  • DOI: https://doi.org/10.1016/j.bmcl.2009.01.055
  • Primary Citation of Related Structures:  
    3DV1, 3DV5

  • PubMed Abstract: 

    The macrocyclic peptidic BACE-1 inhibitors 2a-c show moderate enzymatic and cellular activity. By exchange of the hydroxyethylene- to ethanolamine-transition state mimetic the peptidic character was reduced, providing the highly potent and selective inhibitor 3. Variation of the P' moiety resulted in the macrocyclic inhibitor 14. Both macrocycles show inhibition of BACE-1 in the brain of APP51/16 transgenic mice, 3 (NB-544) after intravenous and 14 (NB-533) after oral application.


  • Organizational Affiliation

    Novartis Institutes for BioMedical Research, Novartis Pharma AG, PO Box, CH-4002 Basel, Switzerland.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-secretase 1
A, B, C
402Homo sapiensMutation(s): 0 
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
AR9
Query on AR9

Download Ideal Coordinates CCD File 
D [auth A],
E [auth B],
F [auth C]
(2R,4S)-N-butyl-4-[(2S,5S,7R)-2,7-dimethyl-3,15-dioxo-1,4-diazacyclopentadecan-5-yl]-4-hydroxy-2-methylbutanamide
C24 H45 N3 O4
ZUIGWVKXPZANDI-MJCUULBUSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
AR9 PDBBind:  3DV1 IC50: 590 (nM) from 1 assay(s)
BindingDB:  3DV1 IC50: min: 590, max: 1.00e+4 (nM) from 2 assay(s)
Binding MOAD:  3DV1 IC50: 590 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.241 
  • R-Value Work: 0.207 
  • R-Value Observed: 0.223 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 82.027α = 90
b = 102.945β = 103.66
c = 99.916γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
PDB_EXTRACTdata extraction
MAR345data collection
CNXphasing
CNXrefinement

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-02-24
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-10-25
    Changes: Refinement description
  • Version 1.3: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description