› 3ufl

X-ray diffraction
1.9Å resolution

Discovery of Pyrrolidine-based b-Secretase Inhibitors: Lead Advancement through Conformational Design for Maintenance of Ligand Binding Efficiency

Released:
DOI: 10.2210/pdb3ufl/pdb
PDB entry 3ufl coloured by chain, front view.
PDB entry 3ufl coloured by chain, side view.
PDB entry 3ufl coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of pyrrolidine-based β-secretase inhibitors: lead advancement through conformational design for maintenance of ligand binding efficiency.
Stachel SJ, Steele TG, Petrocchi A, Haugabook SJ, McGaughey G, Katharine Holloway M, Allison T, Munshi S, Zuck P, Colussi D, Tugasheva K, Wolfe A, Graham SL, Vacca JP
Bioorg Med Chem Lett 22 240-4 (2012)
PMID: 22130130

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: 389 amino acids
Theoretical weight: 43.31 KDa
Source organism: Homo sapiens
Expression system: Not provided
UniProt:
  • Canonical: P56817 (Residues: 58-446; Coverage: 81%)
Gene names: BACE, BACE1, KIAA1149
Sequence domains: Eukaryotic aspartyl protease
Structure domains: Acid Proteases

Ligands and Environments

3 bound ligands:
Ligand 508 1 x 508
Ligand SO4 4 x SO4
Ligand GOL 2 x GOL
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 17-ID
Spacegroup: C2221
Unit cell:
a: 103.668Å b: 127.642Å c: 76.846Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.214 0.212 0.245
Expression system: Not provided

Quick links

Citations

8 review citations

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