› 3rtn

X-ray diffraction
2.7Å resolution

Structure of Bace-1 (Beta-Secretase) in Complex with 3-(2-Amino-6-o-tolylquinolin-3-yl)-N-cyclohexylpropanamide

Released:
DOI: 10.2210/pdb3rtn/pdb
PDB entry 3rtn coloured by chain, front view.
PDB entry 3rtn coloured by chain, side view.
PDB entry 3rtn coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
From fragment screening to in vivo efficacy: optimization of a series of 2-aminoquinolines as potent inhibitors of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1).
Cheng Y, Judd TC, Bartberger MD, Brown J, Chen K, Fremeau RT, Hickman D, Hitchcock SA, Jordan B, Li V, Lopez P, Louie SW, Luo Y, Michelsen K, Nixey T, Powers TS, Rattan C, Sickmier EA, St Jean DJ, Wahl RC, Wen PH, Wood S
J Med Chem 54 5836-57 (2011)
PMID: 21707077

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

3 bound ligands:
Ligand IOD 5 x IOD
Ligand GOL 3 x GOL
Ligand RTN 1 x RTN
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 5.0.2
Spacegroup: P6122
Unit cell:
a: 103.365Å b: 103.365Å c: 170.197Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.223 0.22 0.271
Expression system: Escherichia coli

Quick links

Citations

16 review citations

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

1 mention without citation

Expansion of the structure-activity relationships of BACE1 inhibitors by harnessing diverse building blocks prepared using a unified synthetic approach.
Mayol-Llinàs et al. (2019)