› 4fs4

X-ray diffraction
1.74Å resolution

Structure of BACE Bound to (S)-4-(3'-methoxy-[1,1'-biphenyl]-3-yl)-1,4-dimethyl-6-oxotetrahydropyrimidin-2(1H)-iminium

Released:
DOI: 10.2210/pdb4fs4/pdb
PDB entry 4fs4 coloured by chain, front view.
PDB entry 4fs4 coloured by chain, side view.
PDB entry 4fs4 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
A Potent and Orally Efficacious, Hydroxyethylamine-Based Inhibitor of β-Secretase.
Kaller MR, Harried SS, Albrecht B, Amarante P, Babu-Khan S, Bartberger MD, Brown J, Brown R, Chen K, Cheng Y, Citron M, Croghan MD, Graceffa R, Hickman D, Judd T, Kriemen C, La D, Li V, Lopez P, Luo Y, Masse C, Monenschein H, Nguyen T, Pennington LD, Miguel TS, Sickmier EA, Wahl RC, Weiss MM, Wen PH, Williamson T, Wood S, Xue M, Yang B, Zhang J, Patel V, Zhong W, Hitchcock S
ACS Med Chem Lett 3 886-91 (2012)
PMID: 24900403

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

Assemblies composition:
homo dimer
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: 390 amino acids
Theoretical weight: 43.43 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21
UniProt:
  • Canonical: P56817 (Residues: 58-447; Coverage: 81%)
Gene names: BACE, BACE1, KIAA1149
Sequence domains: Eukaryotic aspartyl protease
Structure domains: Acid Proteases

Ligands and Environments

2 bound ligands:
Ligand H24 2 x H24
Ligand TLA 2 x TLA
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU FR-E DW
Spacegroup: P212121
Unit cell:
a: 86.5Å b: 90.364Å c: 131.146Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.207 0.205 0.233
Expression system: Escherichia coli BL21

Quick links

Citations

3 review citations

Highlighting membrane protein structure and function: A celebration of the Protein Data Bank.
Li et al. (2021)
2 more

4 mentions without citation

Comparison of affinity ranking using AutoDock-GPU and MM-GBSA scores for BACE-1 inhibitors in the D3R Grand Challenge 4.
El Khoury et al. (2019)
3 more