› 2ohs

X-ray diffraction
2.45Å resolution

X-ray crystal structure of beta secretase complexed with compound 6b

Released:
DOI: 10.2210/pdb2ohs/pdb
PDB entry 2ohs coloured by chain, front view.
PDB entry 2ohs coloured by chain, side view.
PDB entry 2ohs coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Application of fragment screening by X-ray crystallography to the discovery of aminopyridines as inhibitors of beta-secretase.
Congreve M, Aharony D, Albert J, Callaghan O, Campbell J, Carr RA, Chessari G, Cowan S, Edwards PD, Frederickson M, McMenamin R, Murray CW, Patel S, Wallis N
J Med Chem 50 1124-32 (2007)
PMID: 17315857

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 Chain: A
Molecule details ›
Chain: A
Length: 402 amino acids
Theoretical weight: 44.84 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P56817 (Residues: 45-446; Coverage: 84%)
Gene names: BACE, BACE1, KIAA1149
Sequence domains: Eukaryotic aspartyl protease
Structure domains: Acid Proteases

Ligands and Environments

3 bound ligands:
Ligand IOD 2 x IOD
Ligand DMS 1 x DMS
Ligand 9IP 1 x 9IP
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ESRF BEAMLINE ID14-3
Spacegroup: P6122
Unit cell:
a: 101.303Å b: 101.303Å c: 170.355Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.185 0.182 0.251
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

19 review citations

The influence of lead discovery strategies on the properties of drug candidates.
Keserü et al. (2009)
18 more

3 mentions without citation

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