› 3r2f

X-ray diffraction
2.53Å resolution

Crystal structure of beta-site app-cleaving enzyme 1 (BACE-WT) complex with BMS-693391 AKA (2S)-2-((3R)-3-acetamido-3-isobutyl-2-oxo-1-pyrrolidinyl)-N-((1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-2-((2R,4R)-4-propoxy-2-pyrrolidinyl)ethyl)-4-phenylbutanamide

Released:
DOI: 10.2210/pdb3r2f/pdb
PDB entry 3r2f coloured by chain, front view.
PDB entry 3r2f coloured by chain, side view.
PDB entry 3r2f coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Monosubstituted γ-lactam and conformationally constrained 1,3-diaminopropan-2-ol transition-state isostere inhibitors of β-secretase (BACE).
Boy KM, Guernon JM, Shi J, Toyn JH, Meredith JE, Barten DM, Burton CR, Albright CF, Marcinkeviciene J, Good AC, Tebben AJ, Muckelbauer JK, Camac DM, Lentz KA, Bronson JJ, Olson RE, Macor JE, Thompson LA
Bioorg Med Chem Lett 21 6916-24 (2011)
PMID: 21782431

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 Chains: A, B, D, E
Molecule details ›
Chains: A, B, D, E
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

1 bound ligand:
Ligand PB0 4 x PB0
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU FR-E SUPERBRIGHT
Spacegroup: P21
Unit cell:
a: 86.306Å b: 130.255Å c: 86.927Å
α: 90° β: 96.53° γ: 90°
R-values:
R R work R free
0.283 0.28 0.33
Expression system: Escherichia coli

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

Collateral Sensitivity of Parthenolide via NF-κB and HIF-α Inhibition and Epigenetic Changes in Drug-Resistant Cancer Cell Lines.
Dawood et al. (2019)