› 2vnn

X-ray diffraction
1.87Å resolution

Human BACE-1 in complex with 7-ethyl-N-((1S,2R)-2-hydroxy-1-(phenylmethyl)-3-(((3-(trifluoromethyl)phenyl)methyl)amino)propyl)-1- methyl-3,4-dihydro-1H-(1,2,5)thiadiazepino(3,4,5-hi)indole-9- carboxamide 2,2-dioxide

Released:
DOI: 10.2210/pdb2vnn/pdb
PDB entry 2vnn coloured by chain, front view.
PDB entry 2vnn coloured by chain, side view.
PDB entry 2vnn coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Second generation of hydroxyethylamine BACE-1 inhibitors: optimizing potency and oral bioavailability.
Charrier N, Clarke B, Cutler L, Demont E, Dingwall C, Dunsdon R, East P, Hawkins J, Howes C, Hussain I, Jeffrey P, 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
J Med Chem 51 3313-7 (2008)
PMID: 18457381

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 CM7 1 x CM7
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ESRF BEAMLINE ID23-1
Spacegroup: P212121
Unit cell:
a: 48.469Å b: 76.699Å c: 104.174Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.174 0.173 0.211
Expression system: Cricetulus griseus

Quick links

Citations

4 review citations

Developing β-secretase inhibitors for treatment of Alzheimer's disease.
Ghosh et al. (2012)
3 more

2 mentions without citation

Exploring the binding of BACE-1 inhibitors using comparative binding energy analysis (COMBINE).
Liu et al. (2012)
1 more