› 2fdp

X-ray diffraction
2.5Å resolution

Crystal structure of beta-secretase complexed with an amino-ethylene inhibitor

Released:
DOI: 10.2210/pdb2fdp/pdb
PDB entry 2fdp coloured by chain, front view.
PDB entry 2fdp coloured by chain, side view.
PDB entry 2fdp coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Aminoethylenes: a tetrahedral intermediate isostere yielding potent inhibitors of the aspartyl protease BACE-1.
Yang W, Lu W, Lu Y, Zhong M, Sun J, Thomas AE, Wilkinson JM, Fucini RV, Lam M, Randal M, Shi XP, Jacobs JW, McDowell RS, Gordon EM, Ballinger MD
J Med Chem 49 839-42 (2006)
PMID: 16451048

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 domain:

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: 388 amino acids
Theoretical weight: 43.26 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21
UniProt:
  • Canonical: P56817 (Residues: 59-446; Coverage: 81%)
Gene names: BACE, BACE1, KIAA1149
Sequence domains: Eukaryotic aspartyl protease
Structure domains: Acid Proteases

Ligands and Environments

1 bound ligand:
Ligand FRP 3 x FRP
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRL BEAMLINE BL1-5
Spacegroup: P21
Unit cell:
a: 81.189Å b: 102.188Å c: 99.53Å
α: 90° β: 103.21° γ: 90°
R-values:
R R work R free
0.227 0.225 0.254
Expression system: Escherichia coli BL21

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Citations

7 review citations

Recent advances in the multitarget-directed ligands approach for the treatment of Alzheimer's disease.
León et al. (2013)
6 more

9 mentions without citation

Application of the PM6 semi-empirical method to modeling proteins enhances docking accuracy of AutoDock.
Bikadi et al. (2009)
8 more