› 3ivh

X-ray diffraction
1.8Å resolution

Design and Synthesis of Potent BACE-1 Inhibitors with Cellular Activity: Structure-Activity Relationship of P1 Substituents

Released:
DOI: 10.2210/pdb3ivh/pdb
PDB entry 3ivh coloured by chain, front view.
PDB entry 3ivh coloured by chain, side view.
PDB entry 3ivh coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Design and synthesis of cell potent BACE-1 inhibitors: structure-activity relationship of P1' substituents.
Sealy JM, Truong AP, Tso L, Probst GD, Aquino J, Hom RK, Jagodzinska BM, Dressen D, Wone DW, Brogley L, John V, Tung JS, Pleiss MA, Tucker JA, Konradi AW, Dappen MS, Toth G, Pan H, Ruslim L, Miller J, Bova MP, Sinha S, Quinn KP, Sauer JM
Bioorg Med Chem Lett 19 6386-91 (2009)
PMID: 19811916

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: 406 amino acids
Theoretical weight: 45.45 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P56817 (Residues: 57-453; Coverage: 83%)
Gene names: BACE, BACE1, KIAA1149
Sequence domains: Eukaryotic aspartyl protease
Structure domains: Acid Proteases

Ligands and Environments

1 bound ligand:
Ligand 1LI 1 x 1LI
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 8.3.1
Spacegroup: C2
Unit cell:
a: 72.924Å b: 105.181Å c: 51.029Å
α: 90° β: 95.25° γ: 90°
R-values:
R R work R free
0.208 0.206 0.249
Expression system: Escherichia coli

Quick links

Citations

3 review citations

Developing β-secretase inhibitors for treatment of Alzheimer's disease.
Ghosh et al. (2012)
2 more

2 mentions without citation

Fragment-based Binding Efficiency Indices in Bioactive Molecular Design: A Computational Approach to BACE-1 Inhibitors.
Razzaghi-Asl et al. (2013)
1 more