› 4r95

X-ray diffraction
1.99Å resolution

BACE-1 in complex with 2-(((1R,3S)-3-(((R)-4-(2-cyclohexylethyl)-2-iminio-1-methyl-5-oxoimidazolidin-4-yl)methyl)cyclohexyl)amino)quinolin-1-ium

Released:
DOI: 10.2210/pdb4r95/pdb
PDB entry 4r95 coloured by chain, front view.
PDB entry 4r95 coloured by chain, side view.
PDB entry 4r95 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of potent iminoheterocycle BACE1 inhibitors.
Caldwell JP, Mazzola RD, Durkin J, Chen J, Chen X, Favreau L, Kennedy M, Kuvelkar R, Lee J, McHugh N, McKittrick B, Orth P, Stamford A, Strickland C, Voigt J, Wang L, Zhang L, Zhang Q, Zhu Z
Bioorg Med Chem Lett 24 5455-9 (2014)
PMID: 25455483

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
Molecule details ›
Chains: A, B
Length: 414 amino acids
Theoretical weight: 46.25 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P56817 (Residues: 41-454; Coverage: 86%)
Gene names: BACE, BACE1, KIAA1149
Sequence domains: Eukaryotic aspartyl protease
Structure domains: Acid Proteases

Ligands and Environments

2 bound ligands:
Ligand TLA 3 x TLA
Ligand 3KW 2 x 3KW
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU RU200
Spacegroup: P212121
Unit cell:
a: 86.46Å b: 89.48Å c: 130.79Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.192 0.191 0.216
Expression system: Escherichia coli

Quick links

Citations

2 review citations

Development and Structural Modification of BACE1 Inhibitors.
Gu et al. (2016)
1 more