› 5he5

X-ray diffraction
1.55Å resolution

BACE-1 in complex with (7aR)-7a-(5-cyanothiophen-2-yl)-6-(5-fluoro-4-methyl-6-(methylamino)pyrimidin-2-yl)-3-methyl-4-oxooctahydro-2H-pyrrolo[3,4-d]pyrimidin-2-iminium

Released:
DOI: 10.2210/pdb5he5/pdb
PDB 5he5 coloured by chain and viewed from the front.
PDB 5he5 coloured by chain and viewed from the side.
PDB 5he5 coloured by chain and viewed from the top.
Source organism: Homo sapiens
Primary publication:
Structure-Based Design of an Iminoheterocyclic beta-Site Amyloid Precursor Protein Cleaving Enzyme (BACE) Inhibitor that Lowers Central A�� in non-Human Primates.
Mandal M, Wu Y, Misiaszek J, Li G, Buevich A, Caldwell JP, Liu X, Mazzola RD, Orth P, Strickland C, Voigt J, Wang H, Zhu Z, Chen X, Grzelak M, Hyde LA, Kuvelkar R, Leach PT, Terracina G, Zhang L, Zhang Q, Michener MS, Smith B, Cox K, Grotz D, Favreau L, Mitra K, Kazakevich I, McKittrick BA, Greenlee W, Kennedy ME, Parker EM, Cumming JN, Stamford AW
J. Med. Chem. (2016)
PMID: 26937601

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:
  • not assigned
Biological process:
  • not assigned
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Beta-secretase 1 Chains: A, B
Molecule details ›
Chains: A, B
Length: 414 amino acids
Theoretical weight: 46.25 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P56817 (Residues: 41-454; Coverage: 86%)
Gene names: BACE, BACE1, KIAA1149
Sequence domains: Eukaryotic aspartyl protease
Structure domains: Acid Proteases

Ligands and Environments

2 bound ligands:
Ligand TLA 2 x TLA
Ligand 60S 2 x 60S
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 17-ID
Spacegroup: P212121
Unit cell:
a: 86.458Å b: 89.308Å c: 131.437Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.186 0.185 0.201
Expression system: Escherichia coli

Quick links

Citations

5 review citations

Structural biology of cell surface receptors implicated in Alzheimer's disease.
Hermans et al. (2022)
4 more