› 5tol

X-ray diffraction
2.51Å resolution

CRYSTAL STRUCTURE OF BETA-SITE APP-CLEAVING ENZYME 1 COMPLEXED WITH N-(3-((4AS,7AS)-2-AMINO-4,4A,5,6-TETRAHYDRO-7AH-FURO[2,3-D][1,3]THIAZIN-7A-YL)-4-FLUOROPHENYL)-5-BROMO-2-PYRIDINECARBOXAMIDE

Released:
DOI: 10.2210/pdb5tol/pdb
PDB entry 5tol coloured by chain, front view.
PDB entry 5tol coloured by chain, side view.
PDB entry 5tol coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of furo[2,3-d][1,3]thiazinamines as beta amyloid cleaving enzyme-1 (BACE1) inhibitors.
Wu YJ, Guernon J, Rajamani R, Toyn JH, Ahlijanian MK, Albright CF, Muckelbauer J, Chang C, Camac D, Macor JE, Thompson LA
Bioorg Med Chem Lett 26 5729-5731 (2016)
PMID: 27816517

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: 412 amino acids
Theoretical weight: 45.92 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P56817 (Residues: 43-454; Coverage: 86%)
Gene names: BACE, BACE1, KIAA1149
Sequence domains: Eukaryotic aspartyl protease
Structure domains: Acid Proteases

Ligands and Environments

1 bound ligand:
Ligand 7H3 1 x 7H3
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 17-ID
Spacegroup: P6122
Unit cell:
a: 101.49Å b: 101.49Å c: 171.237Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.204 0.201 0.257
Expression system: Escherichia coli

Quick links

Citations

1 review citation

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

5 mentions without citation

Metathesis of a UV imido complex: a route to a terminal UV sulfide.
Kelly et al. (2017)
4 more