› 7d2v

X-ray diffraction
2.1Å resolution

Crystal Structure of BACE1 in complex with N-{3-[(5R)-3-amino-2,5-dimethyl-1,1-dioxo-5,6-dihydro-2H-1lambda6,2,4-thiadiazin-5-yl]-4-fluorophenyl}-5-fluoropyridine-2-carboxamide

Released:
DOI: 10.2210/pdb7d2v/pdb
PDB entry 7d2v coloured by chain, front view.
PDB entry 7d2v coloured by chain, side view.
PDB entry 7d2v 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:
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: 416 amino acids
Theoretical weight: 46.39 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

Ligands and Environments

3 bound ligands:
Ligand IOD 3 x IOD
Ligand GOL 2 x GOL
Ligand 66F 1 x 66F
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU FR-E+ SUPERBRIGHT
Spacegroup: P6122
Unit cell:
a: 102.72Å b: 102.72Å c: 170.591Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.21 0.206 0.245
Expression system: Escherichia coli

Quick links

Citations

3 citation in other articles

To Design Scalable Free Energy Perturbation Networks, Optimal Is Not Enough.
Pitman et al. (2023)
2 more

1 mention without citation

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)