| Structural highlights
3exo 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.
| | Ligands: | , , |
| Gene: | BACE1, BACE, 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 small molecule inhibitor of beta-secretase with a unique binding mode has been developed. Crystallographic determination of the enzyme-inhibitor complex shows the catalytic aspartate residues in the active site are not engaged in inhibitor binding. This unprecedented binding mode in the field of aspartyl protease inhibition is described.
Identification of a small molecule beta-secretase inhibitor that binds without catalytic aspartate engagement.,Steele TG, Hills ID, Nomland AA, de Leon P, Allison T, McGaughey G, Colussi D, Tugusheva K, Haugabook SJ, Espeseth AS, Zuck P, Graham SL, Stachel SJ Bioorg Med Chem Lett. 2009 Jan 1;19(1):17-20. Epub 2008 Nov 13. PMID:19036583[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
- ↑ Steele TG, Hills ID, Nomland AA, de Leon P, Allison T, McGaughey G, Colussi D, Tugusheva K, Haugabook SJ, Espeseth AS, Zuck P, Graham SL, Stachel SJ. Identification of a small molecule beta-secretase inhibitor that binds without catalytic aspartate engagement. Bioorg Med Chem Lett. 2009 Jan 1;19(1):17-20. Epub 2008 Nov 13. PMID:19036583 doi:10.1016/j.bmcl.2008.11.027
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