› 4b1c

X-ray diffraction
1.95Å resolution

New Aminoimidazoles as BACE-1 Inhibitors: From Rational Design to Ab- lowering in Brain

Released:
DOI: 10.2210/pdb4b1c/pdb
PDB entry 4b1c coloured by chain, front view.
PDB entry 4b1c coloured by chain, side view.
PDB entry 4b1c coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
New aminoimidazoles as β-secretase (BACE-1) inhibitors showing amyloid-β (Aβ) lowering in brain.
Gravenfors Y, Viklund J, Blid J, Ginman T, Karlström S, Kihlström J, Kolmodin K, Lindström J, von Berg S, von Kieseritzky F, Bogar K, Slivo C, Swahn BM, Olsson LL, Johansson P, Eketjäll S, Fälting J, Jeppsson F, Strömberg K, Janson J, Rahm F
J Med Chem 55 9297-311 (2012)
PMID: 23017051

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: 375 amino acids
Theoretical weight: 41.91 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P56817 (Residues: 56-446; Coverage: 78%)
Gene names: BACE, BACE1, KIAA1149
Sequence domains: Eukaryotic aspartyl protease
Structure domains: Acid Proteases

Ligands and Environments

2 bound ligands:
Ligand DMS 1 x DMS
Ligand 1B1 1 x 1B1
No modified residues

Experiments and Validation Details

Entry percentile scores
Spacegroup: P212121
Unit cell:
a: 47.96Å b: 75.596Å c: 104.523Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.191 0.188 0.245
Expression system: Escherichia coli

Quick links

Citations

8 review citations

BACE1 (β-secretase) inhibitors for the treatment of Alzheimer's disease.
Ghosh et al. (2014)
7 more

1 mention without citation

On the Use of OPEFB-Derived Microcrystalline Cellulose and Nano-Bentonite for Development of Thermoplastic Starch Hybrid Bio-Composites with Improved Performance.
Lai et al. (2021)