› 2wf3

X-ray diffraction
2.08Å resolution

Human BACE-1 in complex with 6-(ethylamino)-N-((1S,2R)-2-hydroxy-3-(((3-(methyloxy)phenyl)methyl)amino)-1-(phenylmethyl)propyl)-1-methyl-1, 3,4,5-tetrahydro-2,1-benzothiazepine-8-carboxamide 2,2-dioxide

Released:
DOI: 10.2210/pdb2wf3/pdb
PDB entry 2wf3 coloured by chain, front view.
PDB entry 2wf3 coloured by chain, side view.
PDB entry 2wf3 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Second generation of BACE-1 inhibitors part 2: Optimisation of the non-prime side substituent.
Charrier N, Clarke B, Demont E, Dingwall C, Dunsdon R, Hawkins J, Hubbard J, Hussain I, Maile G, Matico R, Mosley J, Naylor A, O'Brien A, Redshaw S, Rowland P, Soleil V, Smith KJ, Sweitzer S, Theobald P, Vesey D, Walter DS, Wayne G
Bioorg Med Chem Lett 19 3669-73 (2009)
PMID: 19477642

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: 392 amino acids
Theoretical weight: 43.76 KDa
Source organism: Homo sapiens
Expression system: Cricetulus griseus
UniProt:
  • Canonical: P56817 (Residues: 61-452; Coverage: 82%)
Gene names: BACE, BACE1, KIAA1149
Sequence domains: Eukaryotic aspartyl protease
Structure domains: Acid Proteases

Ligands and Environments

2 bound ligands:
Ligand ZY3 1 x ZY3
Ligand GOL 4 x GOL
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ESRF BEAMLINE ID23-2
Spacegroup: P212121
Unit cell:
a: 48.453Å b: 76.868Å c: 104.478Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.166 0.164 0.217
Expression system: Cricetulus griseus

Quick links

Citations

3 review citations

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

3 mentions without citation

Predicting new indications for approved drugs using a proteochemometric method.
Dakshanamurthy et al. (2012)
2 more