› 4trz

X-ray diffraction
3.25Å resolution

Structure of BACE1 complex with 2-thiophenyl HEA-type inhibitor

Released:
DOI: 10.2210/pdb4trz/pdb
PDB entry 4trz coloured by chain, front view.
PDB entry 4trz coloured by chain, side view.
PDB entry 4trz 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-157556 (preferred)
Entry contents:
2 distinct polypeptide molecules
Macromolecules (2 distinct):
Beta-secretase 1 Chains: A, B, C
Molecule details ›
Chains: A, B, C
Length: 388 amino acids
Theoretical weight: 43.28 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P56817 (Residues: 60-447; Coverage: 81%)
Gene names: BACE, BACE1, KIAA1149
Sequence domains: Eukaryotic aspartyl protease
Structure domains: Acid Proteases
2-thiophenyl HEA-type inhibitor Chains: D, E, F
Molecule details ›
Chains: D, E, F
Length: 4 amino acids
Theoretical weight: 682 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: 81.872Å b: 102.42Å c: 101.587Å
α: 90° β: 103.49° γ: 90°
R-values:
R R work R free
0.265 0.263 0.295
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

1 mention without citation

Partial Characterization of Two Cathepsin D Family Aspartic Peptidases of Clonorchis sinensis.
Kang et al. (2019)