› 4i10

X-ray diffraction
2.07Å resolution

Structure-based design of novel dihydroisoquinoline BACE-1 inhibitors that do not engage the catalytic aspartates

Released:
DOI: 10.2210/pdb4i10/pdb
PDB entry 4i10 coloured by chain, front view.
PDB entry 4i10 coloured by chain, side view.
PDB entry 4i10 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Structure-based design of novel dihydroisoquinoline BACE-1 inhibitors that do not engage the catalytic aspartates.
Bowers S, Xu YZ, Yuan S, Probst GD, Hom RK, Chan W, Konradi AW, Sham HL, Zhu YL, Beroza P, Pan H, Brecht E, Yao N, Lougheed J, Tam D, Ren Z, Ruslim L, Bova MP, Artis DR
Bioorg Med Chem Lett 23 2181-6 (2013)
PMID: 23465612

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

Assemblies composition:
monomeric (preferred)
homo dimer
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: 406 amino acids
Theoretical weight: 45.45 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P56817 (Residues: 57-453; Coverage: 83%)
Gene names: BACE, BACE1, KIAA1149
Sequence domains: Eukaryotic aspartyl protease
Structure domains: Acid Proteases

Ligands and Environments

2 bound ligands:
Ligand ZN 3 x ZN
Ligand 1BS 1 x 1BS
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU MICROMAX-007 HF
Spacegroup: C2221
Unit cell:
a: 75.09Å b: 103.9Å c: 99.72Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.172 0.169 0.228
Expression system: Escherichia coli

Quick links

Citations

5 citation in other articles

Biological and computational evaluation of resveratrol inhibitors against Alzheimer's disease.
Koukoulitsa et al. (2016)
4 more

1 mention without citation

Allosteric binding sites in Rab11 for potential drug candidates.
Kumar et al. (2018)