› 3skf

X-ray diffraction
3Å resolution

Crystal structure of beta-site app-cleaving enzyme 1 (BACE-WT) complex with (2S)-2-((3S)-3-(acetylamino)-3-(butan-2-yl)-2-oxopyrrolidin-1-yl)-N-((2S,3R)-3-hydroxy-4-((3-methoxybenzyl)amino)-1-phenylbutan-2-yl)-4-phenylbutanamide

Released:
DOI: 10.2210/pdb3skf/pdb
PDB entry 3skf coloured by chain, front view.
PDB entry 3skf coloured by chain, side view.
PDB entry 3skf coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Synthesis and in vivo evaluation of cyclic diaminopropane BACE-1 inhibitors.
Thompson LA, Shi J, Decicco CP, Tebben AJ, Olson RE, Boy KM, Guernon JM, Good AC, Liauw A, Zheng C, Copeland RA, Combs AP, Trainor GL, Camac DM, Muckelbauer JK, Lentz KA, Grace JE, Burton CR, Toyn JH, Barten DM, Marcinkeviciene J, Meredith JE, Albright CF, Macor JE
Bioorg Med Chem Lett 21 6909-15 (2011)
PMID: 21974952

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 Chains: A, B
Molecule details ›
Chains: A, B
Length: 455 amino acids
Theoretical weight: 50.22 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P56817 (Residues: 14-454; Coverage: 90%)
Gene names: BACE, BACE1, KIAA1149
Sequence domains: Eukaryotic aspartyl protease
Structure domains: Acid Proteases

Ligands and Environments

2 bound ligands:
Ligand PB7 2 x PB7
Ligand IOD 2 x IOD
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU FR-E DW
Spacegroup: P21212
Unit cell:
a: 90.288Å b: 130.264Å c: 85.871Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.256 0.252 0.313
Expression system: Escherichia coli

Quick links

Citations

3 review citations

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