Structural highlights
3msk is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , |
| Related: | 3msj, 3msl, 3msm |
| Gene: | BACE, BACE1, KIAA1149 (HUMAN) |
| Activity: | Memapsin 2, with EC number 3.4.23.46 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
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 series of 2-aminobenzimidazole inhibitors of BACE1 has been discovered using fragment-based drug discovery (FBDD) techniques. The rapid optimization of these inhibitors using structure-guided medicinal chemistry is discussed.
Fragment-based discovery and optimization of BACE1 inhibitors.,Madden J, Dod JR, Godemann R, Kraemer J, Smith M, Biniszkiewicz M, Hallett DJ, Barker J, Dyekjaer JD, Hesterkamp T Bioorg Med Chem Lett. 2010 Sep 1;20(17):5329-33. Epub 2010 Jun 27. PMID:20656487[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
- ↑ Madden J, Dod JR, Godemann R, Kraemer J, Smith M, Biniszkiewicz M, Hallett DJ, Barker J, Dyekjaer JD, Hesterkamp T. Fragment-based discovery and optimization of BACE1 inhibitors. Bioorg Med Chem Lett. 2010 Sep 1;20(17):5329-33. Epub 2010 Jun 27. PMID:20656487 doi:10.1016/j.bmcl.2010.06.089
