› 4frs

X-ray diffraction
1.7Å resolution

Structure of BACE in complex with (S)-4-(3-chloro-5-(5-(prop-1-yn-1-yl)pyridin-3-yl)thiophen-2-yl)-1,4-dimethyl-6-oxotetrahydropyrimidin-2(1H)-iminium

Released:
DOI: 10.2210/pdb4frs/pdb
PDB entry 4frs coloured by chain, front view.
PDB entry 4frs coloured by chain, side view.
PDB entry 4frs coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of an Orally Available, Brain Penetrant BACE1 Inhibitor that Affords Robust CNS Aβ Reduction.
Stamford AW, Scott JD, Li SW, Babu S, Tadesse D, Hunter R, Wu Y, Misiaszek J, Cumming JN, Gilbert EJ, Huang C, McKittrick BA, Hong L, Guo T, Zhu Z, Strickland C, Orth P, Voigt JH, Kennedy ME, Chen X, Kuvelkar R, Hodgson R, Hyde LA, Cox K, Favreau L, Parker EM, Greenlee WJ
ACS Med Chem Lett 3 897-902 (2012)
PMID: 23412139

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: 395 amino acids
Theoretical weight: 44.02 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P56817 (Residues: 53-447; Coverage: 82%)
Gene names: BACE, BACE1, KIAA1149
Sequence domains: Eukaryotic aspartyl protease
Structure domains: Acid Proteases

Ligands and Environments

1 bound ligand:
Ligand 0V6 2 x 0V6
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU FR-E DW
Spacegroup: P212121
Unit cell:
a: 86.473Å b: 89.495Å c: 131.427Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.202 0.201 0.228
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

13 review citations

Function, therapeutic potential and cell biology of BACE proteases: current status and future prospects.
Vassar et al. (2014)
12 more

2 mentions without citation

Constant pH Molecular Dynamics Reveals pH-Modulated Binding of Two Small-Molecule BACE1 Inhibitors.
Ellis et al. (2016)
1 more