Structural highlights
Function
[BACE1_HUMAN] Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The design and synthesis of a novel series of potent BACE1 hydroxyethylamine inhibitors. These inhibitors feature hydrogen bonding substituents at the C-5 position of the isophthalamide ring with improved selectivity over cathepsin D.
Potent and selective isophthalamide S2 hydroxyethylamine inhibitors of BACE1.,Kortum SW, Benson TE, Bienkowski MJ, Emmons TL, Prince DB, Paddock DJ, Tomasselli AG, Moon JB, LaBorde A, TenBrink RE Bioorg Med Chem Lett. 2007 Jun 15;17(12):3378-83. Epub 2007 Apr 3. PMID:17434734[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lin X, Koelsch G, Wu S, Downs D, Dashti A, Tang J. Human aspartic protease memapsin 2 cleaves the beta-secretase site of beta-amyloid precursor protein. Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1456-60. PMID:10677483
- ↑ Okada H, Zhang W, Peterhoff C, Hwang JC, Nixon RA, Ryu SH, Kim TW. Proteomic identification of sorting nexin 6 as a negative regulator of BACE1-mediated APP processing. FASEB J. 2010 Aug;24(8):2783-94. doi: 10.1096/fj.09-146357. Epub 2010 Mar 30. PMID:20354142 doi:10.1096/fj.09-146357
- ↑ Kortum SW, Benson TE, Bienkowski MJ, Emmons TL, Prince DB, Paddock DJ, Tomasselli AG, Moon JB, LaBorde A, TenBrink RE. Potent and selective isophthalamide S2 hydroxyethylamine inhibitors of BACE1. Bioorg Med Chem Lett. 2007 Jun 15;17(12):3378-83. Epub 2007 Apr 3. PMID:17434734 doi:10.1016/j.bmcl.2007.03.096
