› 2ph6

X-ray diffraction
2Å resolution

Crystal Structure of Human Beta Secretase Complexed with inhibitor

Released:
DOI: 10.2210/pdb2ph6/pdb
PDB entry 2ph6 coloured by chain, front view.
PDB entry 2ph6 coloured by chain, side view.
PDB entry 2ph6 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Design, synthesis, and SAR of macrocyclic tertiary carbinamine BACE-1 inhibitors.
Lindsley SR, Moore KP, Rajapakse HA, Selnick HG, Young MB, Zhu H, Munshi S, Kuo L, McGaughey GB, Colussi D, Crouthamel MC, Lai MT, Pietrak B, Price EA, Sankaranarayanan S, Simon AJ, Seabrook GR, Hazuda DJ, Pudvah NT, Hochman JH, Graham SL, Vacca JP, Nantermet PG
Bioorg Med Chem Lett 17 4057-61 (2007)
PMID: 17482814

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: 405 amino acids
Theoretical weight: 45.12 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
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

2 bound ligands:
Ligand SO4 1 x SO4
Ligand 712 1 x 712
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU MICROMAX-007
Spacegroup: C2221
Unit cell:
a: 103.795Å b: 127.13Å c: 76.205Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.195 0.194 0.218
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

10 review citations

Developing β-secretase inhibitors for treatment of Alzheimer's disease.
Ghosh et al. (2012)
9 more

3 mentions without citation

Exploring the binding of BACE-1 inhibitors using comparative binding energy analysis (COMBINE).
Liu et al. (2012)
2 more