› 3dm6

X-ray diffraction
2.6Å resolution

Beta-secretase 1 complexed with statine-based inhibitor

Released:
DOI: 10.2210/pdb3dm6/pdb
PDB entry 3dm6 coloured by chain, front view.
PDB entry 3dm6 coloured by chain, side view.
PDB entry 3dm6 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Design, synthesis and SAR of potent statine-based BACE-1 inhibitors: exploration of P1 phenoxy and benzyloxy residues.
Bäck M, Nyhlén J, Kvarnström I, Appelgren S, Borkakoti N, Jansson K, Lindberg J, Nyström S, Hallberg A, Rosenquist S, Samuelsson B
Bioorg Med Chem 16 9471-86 (2008)
PMID: 18842420

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: 406 amino acids
Theoretical weight: 45.4 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P56817 (Residues: 41-446; Coverage: 85%)
Gene names: BACE, BACE1, KIAA1149
Sequence domains: Eukaryotic aspartyl protease
Structure domains: Acid Proteases

Ligands and Environments

2 bound ligands:
Ligand 757 3 x 757
Ligand IPA 3 x IPA
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ESRF BEAMLINE ID14-1
Spacegroup: P21
Unit cell:
a: 83.435Å b: 103.017Å c: 103.11Å
α: 90° β: 103.5° γ: 90°
R-values:
R R work R free
0.253 0.223 0.281
Expression system: Escherichia coli

Quick links

Citations

1 review citation

Multidisciplinary approaches for targeting the secretase protein family as a therapeutic route for Alzheimer's disease.
Schaduangrat et al. (2019)
14 other articles

4 mentions without citation

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