› 4fse

X-ray diffraction
2.65Å resolution

crystal structure of beta-site app-cleaving enzyme 1 (bace-wt) complex with N-(N-(4-amino-3,5- dichlorobenzyl)carbamimidoyl)-3-(4-methoxyphenyl)-5- methyl-4-isothiazolecarboxamide

Released:
DOI: 10.2210/pdb4fse/pdb
PDB entry 4fse coloured by chain, front view.
PDB entry 4fse coloured by chain, side view.
PDB entry 4fse coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Acyl guanidine inhibitors of β-secretase (BACE-1): optimization of a micromolar hit to a nanomolar lead via iterative solid- and solution-phase library synthesis.
Gerritz SW, Zhai W, Shi S, Zhu S, Toyn JH, Meredith JE, Iben LG, Burton CR, Albright CF, Good AC, Tebben AJ, Muckelbauer JK, Camac DM, Metzler W, Cook LS, Padmanabha R, Lentz KA, Sofia MJ, Poss MA, Macor JE, Thompson LA
J Med Chem 55 9208-23 (2012)
PMID: 23030502

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 Chains: A, B, D, E
Molecule details ›
Chains: A, B, D, E
Length: 455 amino acids
Theoretical weight: 50.22 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
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 0VA 4 x 0VA
Ligand IOD 9 x IOD
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU
Spacegroup: P21
Unit cell:
a: 86.334Å b: 131.219Å c: 88.947Å
α: 90° β: 97.6° γ: 90°
R-values:
R R work R free
0.22 0.217 0.267
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

11 review citations

BACE1 (β-secretase) inhibitors for the treatment of Alzheimer's disease.
Ghosh et al. (2014)
10 more