› 4dh6

X-ray diffraction
2.5Å resolution

Structure of Bace-1 (Beta-Secretase) in Complex with (2R)-N-((2S,3R)-1-(benzo[d][1,3]dioxol-5-yl)-3-hydroxy-4-((S)-6'-neopentyl-3',4'-dihydrospiro[cyclobutane-1,2'-pyrano[2,3-b]pyridine]-4'-ylamino)butan-2-yl)-2-methoxypropanamide

Released:
DOI: 10.2210/pdb4dh6/pdb
PDB entry 4dh6 coloured by chain, front view.
PDB entry 4dh6 coloured by chain, side view.
PDB entry 4dh6 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Design and preparation of a potent series of hydroxyethylamine containing β-secretase inhibitors that demonstrate robust reduction of central β-amyloid.
Weiss MM, Williamson T, Babu-Khan S, Bartberger MD, Brown J, Chen K, Cheng Y, Citron M, Croghan MD, Dineen TA, Esmay J, Graceffa RF, Harried SS, Hickman D, Hitchcock SA, Horne DB, Huang H, Imbeah-Ampiah R, Judd T, Kaller MR, Kreiman CR, La DS, Li V, Lopez P, Louie S, Monenschein H, Nguyen TT, Pennington LD, Rattan C, San Miguel T, Sickmier EA, Wahl RC, Wen PH, Wood S, Xue Q, Yang BH, Patel VF, Zhong W
J Med Chem 55 9009-24 (2012)
PMID: 22468639

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 8 x IOD
Ligand GOL 2 x GOL
Ligand 0KN 1 x 0KN
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 5.0.2
Spacegroup: P6122
Unit cell:
a: 103.694Å b: 103.694Å c: 168.866Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.231 0.226 0.271
Expression system: Escherichia coli

Quick links

Citations

8 review citations

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

2 mentions without citation

Coffee and caffeine potentiate the antiamyloidogenic activity of melatonin via inhibition of Aβ oligomerization and modulation of the Tau-mediated pathway in N2a/APP cells.
Zhang et al. (2015)
1 more