› 4zsp

X-ray diffraction
1.91Å resolution

BACE crystal structure with bicyclic aminothiazine inhibitor

Released:
DOI: 10.2210/pdb4zsp/pdb
PDB entry 4zsp coloured by chain, front view.
PDB entry 4zsp coloured by chain, side view.
PDB entry 4zsp coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Preparation and biological evaluation of conformationally constrained BACE1 inhibitors.
Winneroski LL, Schiffler MA, Erickson JA, May PC, Monk SA, Timm DE, Audia JE, Beck JP, Boggs LN, Borders AR, Boyer RD, Brier RA, Hudziak KJ, Klimkowski VJ, Garcia Losada P, Mathes BM, Stout SL, Watson BM, Mergott DJ
Bioorg Med Chem 23 3260-8 (2015)
PMID: 26001341

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: 442 amino acids
Theoretical weight: 48.97 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P56817 (Residues: 14-454; Coverage: 90%)
Gene names: BACE, BACE1, KIAA1149
Sequence domains: Eukaryotic aspartyl protease
Structure domains: Acid Proteases

Ligands and Environments

2 bound ligands:
Ligand 4RZ 2 x 4RZ
Ligand GOL 2 x GOL
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 31-ID
Spacegroup: P212121
Unit cell:
a: 86.647Å b: 91.689Å c: 131.205Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.189 0.189 0.243
Expression system: Escherichia coli

Quick links

Citations

3 review citations

Bioactive Thiazine and Benzothiazine Derivatives: Green Synthesis Methods and Their Medicinal Importance.
Badshah et al. (2016)
2 more

2 mentions without citation

Scaffold Hopping Transformations Using Auxiliary Restraints for Calculating Accurate Relative Binding Free Energies.
Zou et al. (2021)
1 more