Beta Secretase 1SGZ

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Beta-secretase, also known as BACE or Memapsin 2, is encoded by the gene BACE1. Beta-secretase is a proteolytic, transmembrane enzyme with two active sites on the extracellular region. It is associated with processing amyloid precursor protein (APP), which is an integral membrane protein.[1] A malfunction in the processing of APP results in the formation of the peptide amyloid beta. Amyloid-beta is a neurotoxic peptide segment that aggregates into plaques. These plaques are the primary component of plaques found in individuals with Alzheimers Disease. [2] Other biological associations of this enzyme include modulating myelination in the central and peripheral nervous systems.[3]

Human Beta-secretase (PDB 1SGZ)

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References

  1. Ghosh, A.; Kumaragurubaran, N.; Hong, L.; Koelsh, G.; Tang, J. Memapsin 2 (Beta-Secretase) Inhibitors: Drug Development. CAR Current Alzheimer Research. [Online] 2008, 5, 121–131. http://jamesmadisonva.library.ingentaconnect.com/content/ben/car/2008/00000005/00000002/art00004
  2. 2.0 2.1 2.2 John, V.; Beck, J. P.; Bienkowski, M. J.; Sinha, S.; Heinrikson, R. L. Human β-Secretase (BACE) And BACE Inhibitors. ChemInform. [Online] 2004, 35, 4625-4630. http://pubs.acs.org/doi/pdf/10.1021/jm030247h
  3. Hu, X.; Hicks, C. W.; He, W.; Wong, P.; Macklin, W. B.; Trapp, B. D.; Yan, R. Bace1 Modulates Myelination in the Central and Peripheral Nervous System. Nature Neuroscience Nat Neurosci. [Online] 2006, 9, 1520–1525. http://www.nature.com/neuro/journal/v9/n12/abs/nn1797.html
  4. Nomenclature Committee of the International Union of Biochemistry and Molecular Biology. The Enzyme List Class 3 — Hydrolases. http://www.enzyme-database.org/downloads/ec3.pdf
  5. DBGET Search. KEGG ENZYME: 3.4.23.46. http://www.genome.jp/dbget-bin/www_bget?ec:3.4.23.46
  6. 6.0 6.1 6.2 Venugopal, C.; Demos, C. M.; Rao, K. S. J.; Pappolla, M. A.; Sambamurti, K. Beta-secretase: Structure, Function, and Evolution. CNS & Neurological Disorders Drug Targets. [Online] 2008. 7(3), 278–294. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2921875/
  7. 7.0 7.1 7.2 Shimizu, H.; Tosaki, A.; Kaneko, K.; Hisano, T.; Sakurai, T.; Nukina, N. Crystal Structure of an Active Form of BACE1, an Enzyme Responsible for Amyloid Beta Protein Production. Molecular and Cellular Biology [Online] 2008, 28(11), 3663-671. http://mcb.asm.org/content/28/11/3663.full.pdf+html
  8. Kumalo, M.; Soumendranath B.; Soliman, M. E. Investigation of Flap Flexibility of β-secretase Using Molecular Dynamic Simulations. Journal of Biomolecular Structure and Dynamics [Online] , 2015, 1-12. http://www.tandfonline.com/doi/full/10.1080/07391102.2015.1064831
  9. 9.0 9.1 9.2 Golub, M. (Producer) & Golub, M. (Director). (2015). Youtube. United States: University of Rochester Introductory Biochemistry
  10. 10.0 10.1 Manada, N., Tanokashira, D., Hoska, A., Kametani, F., Tamoka, A,. and Araki, W. (2015). Amyloid beta-protein oligomers upregulate the beta-secretase, BACE1, through a post-translational mechanism involving its altered subcellular distribution in neurons. Molecular Brain, Vol. 8, p.1-12. 12p. doi: 10.1186/s13041-015-0163-5
  11. Sugana, K., Padlan E., Smith, C., Carlson, W., and Davis, D. (1987). Retrieved April 5, 2016 from 510px-Aspartyl_protease_mechanism.png
  12. JCSciphile, March - Beta-Secretase, 2014, Web, Retrieved April 5, 2016 from http://jcsciphile.com/molecule-of-the-month/march-beta-secretase/
  13. Vasser, R. The B-Secretase Enzyme in Alzheimer’s Disease. Journal of Molecular Neurosceince. 2004, 23, 105-113. http://link.springer.com/article/10.1385/JMN:23:1-2:105
  14. Shoji, M.; Golde, T.; Ghiso, J.; Cheung, T.; Estus, S.; Shaffer, L.; Cai, X.; Mckay, D.; Tintner, R.; Frangione, B.; Et, A. Production Of the Alzheimer Amyloid-beta Protein by Normal Proteolytic Processing. Science. 1992, 258, 126–129.
  15. AnaSpec. Amyloid Peptides. Peptides, http://www.anaspec.com/products/productcategory.asp?id=1
  16. Thompson, L.; Bronson, J.; Zusi, C.; Progress in the discovery of BACE Inhibitors. Current Pharmaceutical design. 2005, 11, 3383-3404
  17. 17.0 17.1 Ghosh, A. K.; Brindisi, M.; Tang, J. Developing β-Secretase Inhibitors for Treatment of Alzheimer’s Disease. Journal of Neurochemistry. [Online] 2011, 120, 71–83.http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2011.07476.x/full

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