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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BACE1

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Crystal structure of BACE1 with its inhibitor, 4ivs
Ligands:	VSI
Activity:	Memapsin 2, with EC number 3.4.23.46
Related:	4ivt
Resources:	FirstGlance, OCA, RCSB, PDBsum
Coordinates:	save as pdb, mmCIF, xml

Structures

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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 (residues 93-96) and DSGT (residues 289-292), 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 six luminal cysteine residues that form three intramolecular disulfide bonds and several N-linked glycosylation sites