› 5kr8

X-ray diffraction
2.12Å resolution

(4~{S},6~{S})-4-[2,4-bis(fluoranyl)phenyl]-6-(3,5-dimethyl-1,2-oxazol-4-yl)-4-methyl-5,6-dihydro-1,3-thiazin-2-amine (compound 5) bound to BACE1

Released:
DOI: 10.2210/pdb5kr8/pdb
PDB entry 5kr8 coloured by chain, front view.
PDB entry 5kr8 coloured by chain, side view.
PDB entry 5kr8 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery of S3-Truncated, C-6 Heteroaryl Substituted Aminothiazine β-Site APP Cleaving Enzyme-1 (BACE1) Inhibitors.
Wu YJ, Guernon J, Shi J, Marcin L, Higgins M, Rajamani R, Muckelbauer J, Lewis H, Chang C, Camac D, Toyn JH, Ahlijanian MK, Albright CF, Macor JE, Thompson LA
J Med Chem 59 8593-600 (2016)
PMID: 27559936

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: 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 IOD 1 x IOD
Ligand 6WE 1 x 6WE
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: CLSI BEAMLINE 08ID-1
Spacegroup: P6122
Unit cell:
a: 102.059Å b: 102.059Å c: 170.843Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.214 0.213 0.244
Expression system: Escherichia coli

Quick links

Citations

1 review citation

Highlights in BACE1 Inhibitors for Alzheimer's Disease Treatment.
Coimbra et al. (2018)
1 other article