› 3ohh

X-ray diffraction
2.01Å resolution

Crystal structure of beta-site app-cleaving enzyme 1 (bace-wt) complex with bms-681889 aka n~1~-butyl-5-cyano- n~3~-((1s,2r)-1-(3,5-difluorobenzyl)-2-hydroxy-3-((3- methoxybenzyl)amino)propyl)-n~1~-methyl-1h-indole-1,3- dicarboxamide

Released:
DOI: 10.2210/pdb3ohh/pdb
PDB entry 3ohh coloured by chain, front view.
PDB entry 3ohh coloured by chain, side view.
PDB entry 3ohh coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Synthesis and SAR of indole-and 7-azaindole-1,3-dicarboxamide hydroxyethylamine inhibitors of BACE-1.
Marcin LR, Higgins MA, Zusi FC, Zhang Y, Dee MF, Parker MF, Muckelbauer JK, Camac DM, Morin PE, Ramamurthy V, Tebben AJ, Lentz KA, Grace JE, Marcinkeviciene JA, Kopcho LM, Burton CR, Barten DM, Toyn JH, Meredith JE, Albright CF, Bronson JJ, Macor JE, Thompson LA
Bioorg Med Chem Lett 21 537-41 (2011)
PMID: 21078556

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

Assemblies composition:
homo dimer
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-157541 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Beta-secretase 1 Chains: A, B
Molecule details ›
Chains: A, B
Length: 455 amino acids
Theoretical weight: 50.22 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P56817 (Residues: 14-454; Coverage: 90%)
Gene names: BACE, BACE1, KIAA1149
Sequence domains: Eukaryotic aspartyl protease
Structure domains: Acid Proteases

Ligands and Environments

3 bound ligands:
Ligand 3HH 2 x 3HH
Ligand SO4 2 x SO4
Ligand GOL 3 x GOL
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU FR-E SUPERBRIGHT
Spacegroup: C2
Unit cell:
a: 92.177Å b: 86.551Å c: 130.448Å
α: 90° β: 100.45° γ: 90°
R-values:
R R work R free
0.173 0.171 0.213
Expression system: Escherichia coli

Quick links

Citations

2 review citations

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

1 mention without citation

Application of computational methods for the design of BACE-1 inhibitors: validation of in silico modelling.
Bajda et al. (2014)