› 4pzw

X-ray diffraction
1.8Å resolution

Synthesis, Characterization and PK/PD Studies of a Series of Spirocyclic Pyranochromene BACE1 Inhibitors

Released:
DOI: 10.2210/pdb4pzw/pdb
PDB entry 4pzw coloured by chain, front view.
PDB entry 4pzw coloured by chain, side view.
PDB entry 4pzw coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Synthesis, characterization, and PK/PD studies of a series of spirocyclic pyranochromene BACE1 inhibitors.
Volgraf M, Chan L, Huestis MP, Purkey HE, Burkard M, Geck Do M, Harris J, Hunt KW, Liu X, Lyssikatos JP, Rana S, Thomas AA, Vigers GP, Siu M
Bioorg Med Chem Lett 24 2477-80 (2014)
PMID: 24780121

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 2X4 1 x 2X4
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU FR-E SUPERBRIGHT
Spacegroup: C2221
Unit cell:
a: 75.17Å b: 103.94Å c: 99.73Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.204 0.202 0.231
Expression system: Escherichia coli

Quick links

Citations

2 review citations

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