› 7f1d

X-ray diffraction
2.05Å resolution

Crystal Structure of BACE1 in complex with N-{3-[(4R,5R,6R)-2-amino-5-fluoro-4,6-dimethyl-5,6-dihydro-4H-1,3-thiazin-4-yl]-4-fluorophenyl}-2H,3H-[1,4]dioxino[2,3-c]pyridine-7-carboxamide

Released:
DOI: 10.2210/pdb7f1d/pdb
PDB entry 7f1d coloured by chain, front view.
PDB entry 7f1d coloured by chain, side view.
PDB entry 7f1d coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of Extremely Selective Fused Pyridine-Derived β-Site Amyloid Precursor Protein-Cleaving Enzyme (BACE1) Inhibitors with High In Vivo Efficacy through 10s Loop Interactions.
Ueno T, Matsuoka E, Asada N, Yamamoto S, Kanegawa N, Ito M, Ito H, Moechars D, Rombouts FJR, Gijsen HJM, Kusakabe KI
J Med Chem 64 14165-14174 (2021)
PMID: 34553947

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

2 bound ligands:
Ligand IOD 4 x IOD
Ligand 0QQ 1 x 0QQ
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU MICROMAX-007 HF
Spacegroup: P6122
Unit cell:
a: 102.057Å b: 102.057Å c: 170.262Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.2 0.198 0.222
Expression system: Escherichia coli

Quick links

Citations

1 mention without citation

Bayesian models for pooling microarray studies with multiple sources of replications.
Conlon et al. (2006)