› 4trw

X-ray diffraction
2.85Å resolution

Structure of BACE1 complex with a syn-HEA-type inhibitor

Released:
DOI: 10.2210/pdb4trw/pdb
PDB entry 4trw coloured by chain, front view.
PDB entry 4trw coloured by chain, side view.
PDB entry 4trw coloured by chain, top view.
Source organisms:
Primary publication:
Evaluation of transition-state mimics in a superior BACE1 cleavage sequence as peptide-mimetic BACE1 inhibitors.
Hattori Y, Kobayashi K, Deguchi A, Nohara Y, Akiyama T, Teruya K, Sanjoh A, Nakagawa A, Yamashita E, Akaji K
Bioorg Med Chem 23 5626-40 (2015)
PMID: 26264846

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:
hetero dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-157554 (preferred)
Entry contents:
2 distinct polypeptide molecules
Macromolecules (2 distinct):
Beta-secretase 1 Chains: A, B, C
Molecule details ›
Chains: A, B, C
Length: 390 amino acids
Theoretical weight: 43.43 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P56817 (Residues: 58-447; Coverage: 81%)
Gene names: BACE, BACE1, KIAA1149
Sequence domains: Eukaryotic aspartyl protease
Structure domains: Acid Proteases
L-alpha-glutamyl-L-isoleucyl-N-[(2R,3S)-1-{[(1S)-1-carboxybutyl]amino}-2-hydroxy-5-methylhexan-3-yl]-3-thiophen-2-yl-L-alaninamide Chains: D, E, F
Molecule details ›
Chains: D, E, F
Length: 4 amino acids
Theoretical weight: 642 Da
Source organism: synthetic construct
Expression system: Not provided

Ligands and Environments

No bound ligands
1 modified residue:
Ligand TIH 3 x TIH

Experiments and Validation Details

Entry percentile scores
X-ray source: SPRING-8 BEAMLINE BL44XU
Spacegroup: P21
Unit cell:
a: 82.285Å b: 103.661Å c: 102Å
α: 90° β: 102.73° γ: 90°
R-values:
R R work R free
0.208 0.208 0.238
Expression systems:
  • Escherichia coli BL21(DE3)
  • Not provided

Quick links

Citations

1 review citation

Development and Structural Modification of BACE1 Inhibitors.
Gu et al. (2016)
3 other articles