› 4d83

X-ray diffraction
2.4Å resolution

Crystal Structure of Human Beta Secretase in Complex with NVP-BUR436, derived from a co-crystallization experiment

Released:
DOI: 10.2210/pdb4d83/pdb
PDB entry 4d83 coloured by chain, front view.
PDB entry 4d83 coloured by chain, side view.
PDB entry 4d83 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of cyclic sulfone hydroxyethylamines as potent and selective β-site APP-cleaving enzyme 1 (BACE1) inhibitors: structure-based design and in vivo reduction of amyloid β-peptides.
Rueeger H, Lueoend R, Rogel O, Rondeau JM, Möbitz H, Machauer R, Jacobson L, Staufenbiel M, Desrayaud S, Neumann U
J Med Chem 55 3364-86 (2012)
PMID: 22380629

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 Chains: A, B, C
Molecule details ›
Chains: A, B, C
Length: 402 amino acids
Theoretical weight: 44.78 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P56817 (Residues: 48-447; Coverage: 83%)
Gene names: BACE, BACE1, KIAA1149
Sequence domains: Eukaryotic aspartyl protease
Structure domains: Acid Proteases

Ligands and Environments

1 bound ligand:
Ligand 0GT 3 x 0GT
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU FR-E SUPERBRIGHT
Spacegroup: P21
Unit cell:
a: 81.946Å b: 102.893Å c: 100.2Å
α: 90° β: 103.99° γ: 90°
R-values:
R R work R free
0.198 0.196 0.226
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

7 review citations

BACE1 (β-secretase) inhibitors for the treatment of Alzheimer's disease.
Ghosh et al. (2014)
6 more

1 mention without citation

N,N'-Diphenyldithiomalonodiamide: Structural Features, Acidic Properties, and In Silico Estimation of Biological Activity.
Sinotsko et al. (2021)