› 4zpf

X-ray diffraction
1.8Å resolution

BACE1 in complex with 8-(3-((1-aminopropan-2-yl)oxy)benzyl)-4-(cyclohexylamino)-1-(3-fluorophenyl)-1,3,8-triazaspiro[4.5]dec-3-en-2-one

Released:
DOI: 10.2210/pdb4zpf/pdb
PDB entry 4zpf coloured by chain, front view.
PDB entry 4zpf coloured by chain, side view.
PDB entry 4zpf coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Methyl-substitution of an iminohydantoin spiropiperidine β-secretase (BACE-1) inhibitor has a profound effect on its potency.
Egbertson M, McGaughey GB, Pitzenberger SM, Stauffer SR, Coburn CA, Stachel SJ, Yang W, Barrow JC, Neilson LA, McWherter M, Perlow D, Fahr B, Munshi S, Allison TJ, Holloway K, Selnick HG, Yang Z, Swestock J, Simon AJ, Sankaranarayanan S, Colussi D, Tugusheva K, Lai MT, Pietrak B, Haugabook S, Jin L, Chen IW, Holahan M, Stranieri-Michener M, Cook JJ, Vacca J, Graham SL
Bioorg Med Chem Lett 25 4812-4819 (2015)
PMID: 26195137

Function and Biology Details

Reaction catalysed: 
Broad endopeptidase specificity. Cleaves Glu-Val-Asn-Leu-|-Asp-Ala-Glu-Phe in the Swedish variant of Alzheimer's amyloid precursor protein.
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-157541 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Beta-secretase 1 Chain: A
Molecule details ›
Chain: A
Length: 405 amino acids
Theoretical weight: 45.12 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P56817 (Residues: 43-446; Coverage: 84%)
Gene names: BACE, BACE1, KIAA1149
Sequence domains: Eukaryotic aspartyl protease
Structure domains: Acid Proteases

Ligands and Environments

1 bound ligand:
Ligand 4QD 1 x 4QD
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 17-ID
Spacegroup: C2221
Unit cell:
a: 103.72Å b: 127.403Å c: 77.024Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.182 0.181 0.201
Expression system: Escherichia coli

Quick links

Citations

3 review citations

Current and emerging therapeutic targets of alzheimer's disease for the design of multi-target directed ligands.
Blaikie et al. (2019)
2 more

1 mention without citation

Modeling CAPRI targets 110-120 by template-based and free docking using contact potential and combined scoring function.
Kundrotas et al. (2018)