| Structural highlights
3cib is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| Related: | 2qk5, 2qkj, 2qmd, 3cic, 3cid |
| Gene: | BACE1, BACE (Homo sapiens) |
| 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
Guided by structure-based design, we synthesized two novel series of potent inhibitors of BACE1 and generated extensive SAR around both the prime and non-prime side binding pockets. The key feature of both series is a cyclic amine motif specifically crafted to achieve interactions with both the flap and with the S2' pocket.
Rational design of novel, potent piperazinone and imidazolidinone BACE1 inhibitors.,Cumming JN, Le TX, Babu S, Carroll C, Chen X, Favreau L, Gaspari P, Guo T, Hobbs DW, Huang Y, Iserloh U, Kennedy ME, Kuvelkar R, Li G, Lowrie J, McHugh NA, Ozgur L, Pan J, Parker EM, Saionz K, Stamford AW, Strickland C, Tadesse D, Voigt J, Wang L, Wu Y, Zhang L, Zhang Q Bioorg Med Chem Lett. 2008 Jun 1;18(11):3236-41. Epub 2008 Apr 25. PMID:18468890[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
- ↑ Cumming JN, Le TX, Babu S, Carroll C, Chen X, Favreau L, Gaspari P, Guo T, Hobbs DW, Huang Y, Iserloh U, Kennedy ME, Kuvelkar R, Li G, Lowrie J, McHugh NA, Ozgur L, Pan J, Parker EM, Saionz K, Stamford AW, Strickland C, Tadesse D, Voigt J, Wang L, Wu Y, Zhang L, Zhang Q. Rational design of novel, potent piperazinone and imidazolidinone BACE1 inhibitors. Bioorg Med Chem Lett. 2008 Jun 1;18(11):3236-41. Epub 2008 Apr 25. PMID:18468890 doi:http://dx.doi.org/10.1016/j.bmcl.2008.04.050
|
