› 2vkm

X-ray diffraction
2.05Å resolution

Crystal structure of GRL-8234 bound to BACE (Beta-secretase)

Released:
DOI: 10.2210/pdb2vkm/pdb
PDB entry 2vkm coloured by chain, front view.
PDB entry 2vkm coloured by chain, side view.
PDB entry 2vkm coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Potent memapsin 2 (beta-secretase) inhibitors: design, synthesis, protein-ligand X-ray structure, and in vivo evaluation.
Ghosh AK, Kumaragurubaran N, Hong L, Kulkarni S, Xu X, Miller HB, Reddy DS, Weerasena V, Turner R, Chang W, Koelsch G, Tang J
Bioorg Med Chem Lett 18 1031-6 (2008)
PMID: 18180160

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)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Beta-secretase 1 Chains: A, B, C, D
Molecule details ›
Chains: A, B, C, D
Length: 389 amino acids
Theoretical weight: 43.31 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21
UniProt:
  • Canonical: P56817 (Residues: 58-446; Coverage: 81%)
Gene names: BACE, BACE1, KIAA1149
Sequence domains: Eukaryotic aspartyl protease
Structure domains: Acid Proteases

Ligands and Environments

1 bound ligand:
Ligand BSD 4 x BSD
No modified residues

Experiments and Validation Details

Entry percentile scores
Spacegroup: P21
Unit cell:
a: 86.704Å b: 130.308Å c: 87.711Å
α: 90° β: 97.41° γ: 90°
R-values:
R R work R free
0.202 0.202 0.242
Expression system: Escherichia coli BL21

Quick links

Citations

16 review citations

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

8 mentions without citation

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