Sandbox Reserved 817

This Sandbox is Reserved from 06/12/2018, through 30/06/2019 for use in the course "Structural Biology" taught by Bruno Kieffer at the University of Strasbourg, ESBS. This reservation includes Sandbox Reserved 1480 through Sandbox Reserved 1543.

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BACE1BACE1

spinqualitylabelsall models PDB ID 4ivs Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
Crystal structure of BACE1 with its inhibitor, 4ivs
Ligands:
Activity:	Memapsin 2, with EC number 3.4.23.46
Related:	4ivt
Resources:	FirstGlance, OCA, RCSB, PDBsum
Coordinates:	save as pdb, mmCIF, xml

StructuresStructures

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The 501 amino acid sequence of BACE1 bears the hallmark features of eukaryotic aspartic proteases of the pepsin family. BACE1 has two aspartic protease active site motifs, DTGS () and DSGT (), and mutation of either aspartic acid renders the enzyme inactive. Like other aspartic proteases, BACE1 has an N-terminal signal sequence (residues 1–21) and a pro-peptide domain (residues 22–45) that are removed post-translationally, so the mature enzyme begins at residue Glu46. Importantly, BACE1 has a single transmembrane domain near its C-terminus (residues 455–480) and a palmitoylated cytoplasmic tail. Thus, BACE1 is a type I membrane rotein with a luminal active site, features predicted for β-secretase. The position of the BACE1 active site within the lumen of intracellular compartments provides the correct topological orientation for cleavage of APP at the β-secretase site. As observed with other aspartic proteases, BACE1 has that form three intramolecular disulfide bonds and several N-linked glycosylation sites

Structurally, BACE1 belongs to the aspartyl protease family, and contains a bilobal structure forming by an N- and a C-terminal domains [12]. Both N- and C-domains are formed by highly twisted â-sheet structures and each domain contributes an aspartic acid to the catalytic module of the enzyme. It is thus proposed that ligands containing a positive charged moiety might be favorable to counteract the negative charged active site.