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]
Publication Abstract from PubMed
Design, synthesis and evaluation of very potent and selective beta-Secretase 2 (memapsin 1, BACE 2) inhibitors are described. The inhibitors were designed specifically to interact with the S2'-site of beta-secretase 2 to provide >170,000-fold selectivity over beta-secretase (BACE 1) and >15,000-fold selectivity over cathepsin D. BACE 2 is implicated in Type 2 diabetes. The studies serve as an important guide to selective BACE 2 inhibitors.
Design of Potent and Highly Selective Inhibitors for Human beta-Secretase 2 (Memapsin 1), a Target for Type 2 Diabetes.,Ghosh AK, Reddy BS, Yen YC, Cardenas E, Rao KV, Downs D, Huang X, Tang J, Mesecar AD Chem Sci. 2016 May 1;7:3117-3122. Epub 2016 Feb 4. PMID:27347366[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Ghosh AK, Reddy BS, Yen YC, Cardenas E, Rao KV, Downs D, Huang X, Tang J, Mesecar AD. Design of Potent and Highly Selective Inhibitors for Human beta-Secretase 2 (Memapsin 1), a Target for Type 2 Diabetes. Chem Sci. 2016 May 1;7:3117-3122. Epub 2016 Feb 4. PMID:27347366 doi:http://dx.doi.org/10.1039/C5SC03718B
