› 3vv8

X-ray diffraction
2.5Å resolution

Crystal structure of beta secetase in complex with 2-amino-3-methyl-6-((1S,2R)-2-(3'-methylbiphenyl-4-yl)cyclopropyl)pyrimidin-4(3H)-one

Released:
DOI: 10.2210/pdb3vv8/pdb
PDB entry 3vv8 coloured by chain, front view.
PDB entry 3vv8 coloured by chain, side view.
PDB entry 3vv8 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Conformational restriction approach to β-secretase (BACE1) inhibitors: effect of a cyclopropane ring to induce an alternative binding mode.
Yonezawa S, Yamamoto T, Yamakawa H, Muto C, Hosono M, Hattori K, Higashino K, Yutsudo T, Iwamoto H, Kondo Y, Sakagami M, Togame H, Tanaka Y, Nakano T, Takemoto H, Arisawa M, Shuto S
J Med Chem 55 8838-58 (2012)
PMID: 22998419

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: 416 amino acids
Theoretical weight: 46.39 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P56817 (Residues: 43-454; Coverage: 86%)
Gene names: BACE, BACE1, KIAA1149
Sequence domains: Eukaryotic aspartyl protease
Structure domains: Acid Proteases

Ligands and Environments

2 bound ligands:
Ligand GOL 1 x GOL
Ligand B02 1 x B02
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU MICROMAX-007 HF
Spacegroup: P6122
Unit cell:
a: 101.92Å b: 101.92Å c: 169.26Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.227 0.224 0.287
Expression system: Escherichia coli

Quick links

Citations

8 review citations

Conformational restriction: an effective tactic in 'follow-on'-based drug discovery.
Fang et al. (2014)
7 more

1 mention without citation

Benchmark Sets for Binding Hot Spot Identification in Fragment-Based Ligand Discovery.
Wakefield et al. (2020)