› 7dcz

X-ray diffraction
2.3Å resolution

Crystal Structure of BACE1 in complex with N-{3-[(4S)-2-amino-4-methyl-4H-1,3-thiazin-4-yl]-4- fluorophenyl}-5-cyanopyridine-2-carboxamide

Released:
DOI: 10.2210/pdb7dcz/pdb
Model geometry
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PDB entry 7dcz coloured by chain, front view.
PDB entry 7dcz coloured by chain, side view.
PDB entry 7dcz coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of Atabecestat (JNJ-54861911): A Thiazine-Based β-Amyloid Precursor Protein Cleaving Enzyme 1 Inhibitor Advanced to the Phase 2b/3 EARLY Clinical Trial.
Koriyama Y, Hori A, Ito H, Yonezawa S, Baba Y, Tanimoto N, Ueno T, Yamamoto S, Yamamoto T, Asada N, Morimoto K, Einaru S, Sakai K, Kanazu T, Matsuda A, Yamaguchi Y, Oguma T, Timmers M, Tritsmans L, Kusakabe KI, Kato A, Sakaguchi G
J Med Chem 64 1873-1888 (2021)
PMID: 33588527

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 4 x IOD
Ligand GOL 1 x GOL
Ligand H3C 1 x H3C
No modified residues

Experiments and Validation Details

wwPDB Validation report is not available for this entry.
X-ray source: RIGAKU MICROMAX-007 HF
Spacegroup: P6122
Unit cell:
a: 101.958Å b: 101.958Å c: 171.653Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.215 0.213 0.255
Expression system: Escherichia coli

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Citations

8 review citations

Recent advances on drug development and emerging therapeutic agents for Alzheimer's disease.
Athar et al. (2021)
7 more

2 mentions without citation

The Food Additive β-Caryophyllene Exerts Its Neuroprotective Effects Through the JAK2-STAT3-BACE1 Pathway.
Zhang et al. (2022)
1 more

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