› 4b78

X-ray diffraction
1.5Å resolution

Aminoimidazoles as BACE-1 Inhibitors: From De Novo Design to Ab- lowering in Brain

Released:
DOI: 10.2210/pdb4b78/pdb
PDB entry 4b78 coloured by chain, front view.
PDB entry 4b78 coloured by chain, side view.
PDB entry 4b78 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Core refinement toward permeable β-secretase (BACE-1) inhibitors with low hERG activity.
Ginman T, Viklund J, Malmström J, Blid J, Emond R, Forsblom R, Johansson A, Kers A, Lake F, Sehgelmeble F, Sterky KJ, Bergh M, Lindgren A, Johansson P, Jeppsson F, Fälting J, Gravenfors Y, Rahm F
J Med Chem 56 4181-205 (2013)
PMID: 23126626

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: 384 amino acids
Theoretical weight: 42.81 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P56817 (Residues: 62-445; Coverage: 80%)
Gene names: BACE, BACE1, KIAA1149
Sequence domains: Eukaryotic aspartyl protease
Structure domains: Acid Proteases

Ligands and Environments

1 bound ligand:
Ligand KGG 1 x KGG
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ESRF BEAMLINE ID23-1
Spacegroup: P212121
Unit cell:
a: 47.697Å b: 74.107Å c: 104.739Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.208 0.206 0.234
Expression system: Escherichia coli

Quick links

Citations

2 review citations

The evolution of amidine-based brain penetrant BACE1 inhibitors.
Oehlrich et al. (2014)
1 more

1 mention without citation

Partial Characterization of Two Cathepsin D Family Aspartic Peptidases of Clonorchis sinensis.
Kang et al. (2019)