› 7d5u

X-ray diffraction
2.04Å resolution

BACE2 xaperone complex with N-{3-[(9S)-7-amino-2,2-difluoro-9-(prop-1-yn-1-yl)-6-oxa-8-azaspiro[3.5]non-7-en-9-yl]-4-fluorophenyl}-5-cyanopyridine-2-carboxamide

Released:
DOI: 10.2210/pdb7d5u/pdb
PDB entry 7d5u coloured by chain, front view.
PDB entry 7d5u coloured by chain, side view.
PDB entry 7d5u coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Structure-Based Approaches to Improving Selectivity through Utilizing Explicit Water Molecules: Discovery of Selective β-Secretase (BACE1) Inhibitors over BACE2.
Fujimoto K, Yoshida S, Tadano G, Asada N, Fuchino K, Suzuki S, Matsuoka E, Yamamoto T, Yamamoto S, Ando S, Kanegawa N, Tonomura Y, Ito H, Moechars D, Rombouts FJR, Gijsen HJM, Kusakabe KI
J Med Chem 64 3075-3085 (2021)
PMID: 33719429

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:
hetero dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-212889 (preferred)
Entry contents:
2 distinct polypeptide molecules
Macromolecules (2 distinct):
Beta-secretase 2 Chain: A
Molecule details ›
Chain: A
Length: 386 amino acids
Theoretical weight: 42.11 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: Q9Y5Z0 (Residues: 75-460; Coverage: 78%)
Gene names: AEPLC, ALP56, ASP21, BACE2, CDA13, UNQ418/PRO852
Sequence domains: Eukaryotic aspartyl protease
xaperone Chain: D
Molecule details ›
Chain: D
Length: 114 amino acids
Theoretical weight: 12.11 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli

Ligands and Environments

1 bound ligand:
Ligand GX6 1 x GX6
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X06SA
Spacegroup: P212121
Unit cell:
a: 62.926Å b: 74.339Å c: 108.389Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.21 0.207 0.254
Expression system: Escherichia coli

Quick links

Citations

3 citation in other articles

Neuroprotective Effects of Phytochemicals against Aluminum Chloride-Induced Alzheimer's Disease through ApoE4/LRP1, Wnt3/β-Catenin/GSK3β, and TLR4/NLRP3 Pathways with Physical and Mental Activities in a Rat Model.
Hamdan et al. (2022)
2 more