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
A novel class of pyridinyl aminohydantoins was designed and prepared as highly potent BACE1 inhibitors. Compound (S)-4g showed excellent potency with IC(50) of 20 nM for BACE1. X-ray crystallography indicated that the interaction between pyridine nitrogen and the tryptophan Trp76 was a key feature in the S2' region of the enzyme that contributed to increased potency.
Pyridinyl aminohydantoins as small molecule BACE1 inhibitors.,Zhou P, Li Y, Fan Y, Wang Z, Chopra R, Olland A, Hu Y, Magolda RL, Pangalos M, Reinhart PH, Turner MJ, Bard J, Malamas MS, Robichaud AJ Bioorg Med Chem Lett. 2010 Apr 1;20(7):2326-9. Epub 2010 Feb 12. PMID:20202842[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
- ↑ Zhou P, Li Y, Fan Y, Wang Z, Chopra R, Olland A, Hu Y, Magolda RL, Pangalos M, Reinhart PH, Turner MJ, Bard J, Malamas MS, Robichaud AJ. Pyridinyl aminohydantoins as small molecule BACE1 inhibitors. Bioorg Med Chem Lett. 2010 Apr 1;20(7):2326-9. Epub 2010 Feb 12. PMID:20202842 doi:10.1016/j.bmcl.2010.01.136
