› 3fkt

X-ray diffraction
1.9Å resolution

Crystal Structure of Human Beta Secretase Complexed with Spiropiperdine Iminohydantoin Inhibitor

Released:
DOI: 10.2210/pdb3fkt/pdb
PDB entry 3fkt coloured by chain, front view.
PDB entry 3fkt coloured by chain, side view.
PDB entry 3fkt coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery and X-ray crystallographic analysis of a spiropiperidine iminohydantoin inhibitor of beta-secretase.
Barrow JC, Stauffer SR, Rittle KE, Ngo PL, Yang Z, Selnick HG, Graham SL, Munshi S, McGaughey GB, Holloway MK, Simon AJ, Price EA, Sankaranarayanan S, Colussi D, Tugusheva K, Lai MT, Espeseth AS, Xu M, Huang Q, Wolfe A, Pietrak B, Zuck P, Levorse DA, Hazuda D, Vacca JP
J Med Chem 51 6259-62 (2008)
PMID: 18811140

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

Assemblies composition:
homo dimer
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: 405 amino acids
Theoretical weight: 45.12 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P56817 (Residues: 43-446; Coverage: 84%)
Gene names: BACE, BACE1, KIAA1149
Sequence domains: Eukaryotic aspartyl protease
Structure domains: Acid Proteases

Ligands and Environments

1 bound ligand:
Ligand SII 1 x SII
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU MICROMAX-007
Spacegroup: C2221
Unit cell:
a: 103.743Å b: 128.042Å c: 76.768Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.183 0.182 0.217
Expression system: Escherichia coli

Quick links

Citations

7 review citations

Chemistry and biology of multicomponent reactions.
Dömling et al. (2012)
6 more

4 mentions without citation

Molecular shape and medicinal chemistry: a perspective.
Nicholls et al. (2010)
3 more