› 3u6a

X-ray diffraction
2.2Å resolution

Rational Design and Synthesis of Aminopiperazinones as Beta Secretase (BACE) Inhibitors

Released:
DOI: 10.2210/pdb3u6a/pdb
PDB entry 3u6a coloured by chain, front view.
PDB entry 3u6a coloured by chain, side view.
PDB entry 3u6a coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Rational design and synthesis of aminopiperazinones as β-secretase (BACE) inhibitors.
Tresadern G, Delgado F, Delgado O, Gijsen H, Macdonald GJ, Moechars D, Rombouts F, Alexander R, Spurlino J, Van Gool M, Vega JA, Trabanco AA
Bioorg Med Chem Lett 21 7255-60 (2011)
PMID: 22071305

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 Chains: A, B, C
Molecule details ›
Chains: A, B, C
Length: 390 amino acids
Theoretical weight: 43.38 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P56817 (Residues: 58-446; Coverage: 81%)
Gene names: BACE, BACE1, KIAA1149
Sequence domains: Eukaryotic aspartyl protease
Structure domains: Acid Proteases

Ligands and Environments

2 bound ligands:
Ligand 18P 3 x 18P
Ligand SO4 9 x SO4
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X06SA
Spacegroup: C2
Unit cell:
a: 225.3Å b: 104.45Å c: 66.76Å
α: 90° β: 102.66° γ: 90°
R-values:
R R work R free
0.188 0.187 0.237
Expression system: Escherichia coli

Quick links

Citations

6 review citations

Small-molecule BACE1 inhibitors: a patent literature review (2006 - 2011).
Probst et al. (2012)
5 more

2 mentions without citation

Coffee and caffeine potentiate the antiamyloidogenic activity of melatonin via inhibition of Aβ oligomerization and modulation of the Tau-mediated pathway in N2a/APP cells.
Zhang et al. (2015)
1 more