› 5ygx

X-ray diffraction
2.2Å resolution

Structure of BACE1 in complex with N-(3-((4R,5R,6S)-2-amino-6-(1,1-difluoroethyl)-5-fluoro-4-methyl-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-5-(fluoromethoxy)pyrazine-2-carboxamide

Released:
DOI: 10.2210/pdb5ygx/pdb
PDB entry 5ygx coloured by chain, front view.
PDB entry 5ygx coloured by chain, side view.
PDB entry 5ygx coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of Potent and Centrally Active 6-Substituted 5-Fluoro-1,3-dihydro-oxazine β-Secretase (BACE1) Inhibitors via Active Conformation Stabilization.
Nakahara K, Fuchino K, Komano K, Asada N, Tadano G, Hasegawa T, Yamamoto T, Sako Y, Ogawa M, Unemura C, Hosono M, Ito H, Sakaguchi G, Ando S, Ohnishi S, Kido Y, Fukushima T, Dhuyvetter D, Borghys H, Gijsen HJM, Yamano Y, Iso Y, Kusakabe KI
J Med Chem 61 5525-5546 (2018)
PMID: 29775538

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
Structure domains: Acid Proteases

Ligands and Environments

4 bound ligands:
Ligand IOD 2 x IOD
Ligand GOL 5 x GOL
Ligand DMS 1 x DMS
Ligand 0B5 1 x 0B5
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU FR-E SUPERBRIGHT
Spacegroup: P6122
Unit cell:
a: 101.55Å b: 101.55Å c: 170.811Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.18 0.178 0.207
Expression system: Escherichia coli

Quick links

Citations

1 review citation

Reagents for Selective Fluoromethylation: A Challenge in Organofluorine Chemistry.
Reichel et al. (2020)
2 other articles

3 mentions without citation

MathDL: mathematical deep learning for D3R Grand Challenge 4.
Nguyen et al. (2020)
2 more