| Structural highlights
Function
[PPAP_HUMAN] A non-specific tyrosine phosphatase that dephosphorylates a diverse number of substrates under acidic conditions (pH 4-6) including alkyl, aryl, and acyl orthophosphate monoesters and phosphorylated proteins. Has lipid phosphatase activity and inactivates lysophosphatidic acid in seminal plasma.[1] [2] [3] [4] Isoform 2: the cellular form also has ecto-5'-nucleotidase activity in dorsal root ganglion (DRG) neurons. Generates adenosine from AMP which acts as a pain suppressor. Acts as a tumor suppressor of prostate cancer through dephosphorylation of ERBB2 and deactivation of MAPK-mediated signaling.[5] [6] [7] [8]
Publication Abstract from PubMed
Many globular and natively disordered proteins can convert into amyloid fibrils. These fibrils are associated with numerous pathologies as well as with normal cellular functions, and frequently form during protein denaturation. Inhibitors of pathological amyloid fibril formation could be useful in the development of therapeutics, provided that the inhibitors were specific enough to avoid interfering with normal processes. Here we show that computer-aided, structure-based design can yield highly specific peptide inhibitors of amyloid formation. Using known atomic structures of segments of amyloid fibrils as templates, we have designed and characterized an all-d-amino-acid inhibitor of the fibril formation of the tau protein associated with Alzheimer's disease, and a non-natural l-amino-acid inhibitor of an amyloid fibril that enhances sexual transmission of human immunodeficiency virus. Our results indicate that peptides from structure-based designs can disrupt the fibril formation of full-length proteins, including those, such as tau protein, that lack fully ordered native structures. Because the inhibiting peptides have been designed on structures of dual-beta-sheet 'steric zippers', the successful inhibition of amyloid fibril formation strengthens the hypothesis that amyloid spines contain steric zippers.
Structure-based design of non-natural amino-acid inhibitors of amyloid fibril formation.,Sievers SA, Karanicolas J, Chang HW, Zhao A, Jiang L, Zirafi O, Stevens JT, Munch J, Baker D, Eisenberg D Nature. 2011 Jun 15. doi: 10.1038/nature10154. PMID:21677644[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tanaka M, Kishi Y, Takanezawa Y, Kakehi Y, Aoki J, Arai H. Prostatic acid phosphatase degrades lysophosphatidic acid in seminal plasma. FEBS Lett. 2004 Jul 30;571(1-3):197-204. PMID:15280042 doi:10.1016/j.febslet.2004.06.083
- ↑ Munch J, Rucker E, Standker L, Adermann K, Goffinet C, Schindler M, Wildum S, Chinnadurai R, Rajan D, Specht A, Gimenez-Gallego G, Sanchez PC, Fowler DM, Koulov A, Kelly JW, Mothes W, Grivel JC, Margolis L, Keppler OT, Forssmann WG, Kirchhoff F. Semen-derived amyloid fibrils drastically enhance HIV infection. Cell. 2007 Dec 14;131(6):1059-71. PMID:18083097 doi:10.1016/j.cell.2007.10.014
- ↑ Hong S, Klein EA, Das Gupta J, Hanke K, Weight CJ, Nguyen C, Gaughan C, Kim KA, Bannert N, Kirchhoff F, Munch J, Silverman RH. Fibrils of prostatic acid phosphatase fragments boost infections with XMRV (xenotropic murine leukemia virus-related virus), a human retrovirus associated with prostate cancer. J Virol. 2009 Jul;83(14):6995-7003. doi: 10.1128/JVI.00268-09. Epub 2009 Apr 29. PMID:19403677 doi:10.1128/JVI.00268-09
- ↑ Chuang TD, Chen SJ, Lin FF, Veeramani S, Kumar S, Batra SK, Tu Y, Lin MF. Human prostatic acid phosphatase, an authentic tyrosine phosphatase, dephosphorylates ErbB-2 and regulates prostate cancer cell growth. J Biol Chem. 2010 Jul 30;285(31):23598-606. doi: 10.1074/jbc.M109.098301. Epub, 2010 May 24. PMID:20498373 doi:10.1074/jbc.M109.098301
- ↑ Tanaka M, Kishi Y, Takanezawa Y, Kakehi Y, Aoki J, Arai H. Prostatic acid phosphatase degrades lysophosphatidic acid in seminal plasma. FEBS Lett. 2004 Jul 30;571(1-3):197-204. PMID:15280042 doi:10.1016/j.febslet.2004.06.083
- ↑ Munch J, Rucker E, Standker L, Adermann K, Goffinet C, Schindler M, Wildum S, Chinnadurai R, Rajan D, Specht A, Gimenez-Gallego G, Sanchez PC, Fowler DM, Koulov A, Kelly JW, Mothes W, Grivel JC, Margolis L, Keppler OT, Forssmann WG, Kirchhoff F. Semen-derived amyloid fibrils drastically enhance HIV infection. Cell. 2007 Dec 14;131(6):1059-71. PMID:18083097 doi:10.1016/j.cell.2007.10.014
- ↑ Hong S, Klein EA, Das Gupta J, Hanke K, Weight CJ, Nguyen C, Gaughan C, Kim KA, Bannert N, Kirchhoff F, Munch J, Silverman RH. Fibrils of prostatic acid phosphatase fragments boost infections with XMRV (xenotropic murine leukemia virus-related virus), a human retrovirus associated with prostate cancer. J Virol. 2009 Jul;83(14):6995-7003. doi: 10.1128/JVI.00268-09. Epub 2009 Apr 29. PMID:19403677 doi:10.1128/JVI.00268-09
- ↑ Chuang TD, Chen SJ, Lin FF, Veeramani S, Kumar S, Batra SK, Tu Y, Lin MF. Human prostatic acid phosphatase, an authentic tyrosine phosphatase, dephosphorylates ErbB-2 and regulates prostate cancer cell growth. J Biol Chem. 2010 Jul 30;285(31):23598-606. doi: 10.1074/jbc.M109.098301. Epub, 2010 May 24. PMID:20498373 doi:10.1074/jbc.M109.098301
- ↑ Sievers SA, Karanicolas J, Chang HW, Zhao A, Jiang L, Zirafi O, Stevens JT, Munch J, Baker D, Eisenberg D. Structure-based design of non-natural amino-acid inhibitors of amyloid fibril formation. Nature. 2011 Jun 15. doi: 10.1038/nature10154. PMID:21677644 doi:10.1038/nature10154
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