› 2xfk

X-ray diffraction
1.8Å resolution

Human BACE-1 in complex with N-((1S,2R)-3-(((1S)-2-(cyclohexylamino)- 1-methyl-2-oxoethyl)amino)-2-hydroxy-1-(phenylmethyl)propyl)-3-(ethylamino)-5-((methylsulfonyl)(phenyl)amino)benzamide

Released:
DOI: 10.2210/pdb2xfk/pdb
PDB entry 2xfk coloured by chain, front view.
PDB entry 2xfk coloured by chain, side view.
PDB entry 2xfk coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
BACE-1 hydroxyethylamine inhibitors using novel edge-to-face interaction with Arg-296.
Clarke B, Cutler L, Demont E, Dingwall C, Dunsdon R, Hawkins J, Howes C, 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 20 4639-44 (2010)
PMID: 20579874

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

1 bound ligand:
Ligand AA9 1 x AA9
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ESRF BEAMLINE ID14-4
Spacegroup: P212121
Unit cell:
a: 47.864Å b: 76.845Å c: 104.467Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.165 0.163 0.195
Expression system: Cricetulus griseus

Quick links

Citations

2 review citations

Small-molecule BACE1 inhibitors: a patent literature review (2006 - 2011).
Probst et al. (2012)
1 more

1 mention without citation

Structure-based predictions of activity cliffs.
Husby et al. (2015)