› 4j1h

X-ray diffraction
2.2Å resolution

CRYSTAL STRUCTURE OF BACE-1 IN COMPLEX WITH 5-Cyano-pyridine-2-carboxylic acid [3-((4S,6R)-2-amino-4-methyl-6-trifluoromethyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-4-fluoro-phenyl]-amide

Released:
DOI: 10.2210/pdb4j1h/pdb
PDB entry 4j1h coloured by chain, front view.
PDB entry 4j1h coloured by chain, side view.
PDB entry 4j1h coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
β-Secretase (BACE1) inhibitors with high in vivo efficacy suitable for clinical evaluation in Alzheimer's disease.
Hilpert H, Guba W, Woltering TJ, Wostl W, Pinard E, Mauser H, Mayweg AV, Rogers-Evans M, Humm R, Krummenacher D, Muser T, Schnider C, Jacobsen H, Ozmen L, Bergadano A, Banner DW, Hochstrasser R, Kuglstatter A, David-Pierson P, Fischer H, Polara A, Narquizian R
J Med Chem 56 3980-95 (2013)
PMID: 23590342

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: 409 amino acids
Theoretical weight: 45.55 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P56817 (Residues: 46-454; Coverage: 85%)
Gene names: BACE, BACE1, KIAA1149
Sequence domains: Eukaryotic aspartyl protease
Structure domains: Acid Proteases

Ligands and Environments

3 bound ligands:
Ligand NA 2 x NA
Ligand DMS 1 x DMS
Ligand 1HJ 1 x 1HJ
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X10SA
Spacegroup: P6122
Unit cell:
a: 102.685Å b: 102.685Å c: 168.873Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.188 0.186 0.236
Expression system: Escherichia coli

Quick links

Citations

15 review citations

The Genetic Basis of Mendelian Phenotypes: Discoveries, Challenges, and Opportunities.
Chong et al. (2015)
14 more