› 5i3w

X-ray diffraction
2.15Å resolution

Crystal structure of BACE1 in complex with 2-aminooxazoline-3-azaxanthene inhibitor 2

Released:
DOI: 10.2210/pdb5i3w/pdb
PDB entry 5i3w coloured by chain, front view.
PDB entry 5i3w coloured by chain, side view.
PDB entry 5i3w coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Fragment-Linking Approach Using (19)F NMR Spectroscopy To Obtain Highly Potent and Selective Inhibitors of β-Secretase.
Jordan JB, Whittington DA, Bartberger MD, Sickmier EA, Chen K, Cheng Y, Judd T
J Med Chem 59 3732-49 (2016)
PMID: 26978477

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: 411 amino acids
Theoretical weight: 45.82 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P56817 (Residues: 43-453; Coverage: 86%)
Gene names: BACE, BACE1, KIAA1149
Sequence domains: Eukaryotic aspartyl protease
Structure domains: Acid Proteases

Ligands and Environments

4 bound ligands:
Ligand IOD 3 x IOD
Ligand GOL 1 x GOL
Ligand SO4 1 x SO4
Ligand 68L 1 x 68L
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 5.0.2
Spacegroup: P6122
Unit cell:
a: 101.66Å b: 101.66Å c: 172.357Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.182 0.18 0.215
Expression system: Escherichia coli

Quick links

Citations

8 review citations

Highlights in BACE1 Inhibitors for Alzheimer's Disease Treatment.
Coimbra et al. (2018)
7 more

1 mention without citation

Development of 2-aminooxazoline 3-azaxanthene β-amyloid cleaving enzyme (BACE) inhibitors with improved selectivity against Cathepsin D.
Low et al. (2017)