› 4rrn

X-ray diffraction
1.8Å resolution

8-Tetrahydropyran-2-yl chromans: highly selective beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors

Released:
DOI: 10.2210/pdb4rrn/pdb
PDB entry 4rrn coloured by chain, front view.
PDB entry 4rrn coloured by chain, side view.
PDB entry 4rrn coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
8-Tetrahydropyran-2-yl chromans: highly selective beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors.
Thomas AA, Hunt KW, Newhouse B, Watts RJ, Liu X, Vigers G, Smith D, Rhodes SP, Brown KD, Otten JN, Burkard M, Cox AA, Geck Do MK, Dutcher D, Rana S, DeLisle RK, Regal K, Wright AD, Groneberg R, Liao J, Scearce-Levie K, Siu M, Purkey HE, Lyssikatos JP
J Med Chem 57 10112-29 (2014)
PMID: 25411915

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

2 bound ligands:
Ligand NI 1 x NI
Ligand 3UW 1 x 3UW
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU FR-E SUPERBRIGHT
Spacegroup: C2221
Unit cell:
a: 75.47Å b: 103.84Å c: 100.3Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.189 0.188 0.218
Expression system: Escherichia coli

Quick links

Citations

3 review citations

Highlights in BACE1 Inhibitors for Alzheimer's Disease Treatment.
Coimbra et al. (2018)
2 more