Inhibitors of Serine/Threonine Protein Phosphatases: Biochemical and Structural Studies Provide Insight for Further Development

Author(s): Mark R. Swingle, Richard E. Honkanen*

Journal Name: Current Medicinal Chemistry

Volume 26 , Issue 15 , 2019

  Journal Home
Translate in Chinese
Become EABM
Become Reviewer
Call for Editor


Background: The reversible phosphorylation of proteins regulates many key functions in eukaryotic cells. Phosphorylation is catalyzed by protein kinases, with the majority of phosphorylation occurring on side chains of serine and threonine residues. The phosphomonoesters generated by protein kinases are hydrolyzed by protein phosphatases. In the absence of a phosphatase, the half-time for the hydrolysis of alkyl phosphate dianions at 25º C is over 1 trillion years; knon ~2 x 10-20 sec-1. Therefore, ser/thr phosphatases are critical for processes controlled by reversible phosphorylation.

Methods: This review is based on the literature searched in available databases. We compare the catalytic mechanism of PPP-family phosphatases (PPPases) and the interactions of inhibitors that target these enzymes.

Results: PPPases are metal-dependent hydrolases that enhance the rate of hydrolysis ([kcat/kM]/knon ) by a factor of ~1021, placing them among the most powerful known catalysts on earth. Biochemical and structural studies indicate that the remarkable catalytic proficiencies of PPPases are achieved by 10 conserved amino acids, DXH(X)~26DXXDR(X)~20- 26NH(X)~50H(X)~25-45R(X)~30-40H. Six act as metal-coordinating residues. Four position and orient the substrate phosphate. Together, two metal ions and the 10 catalytic residues position the phosphoryl group and an activated bridging water/hydroxide nucleophile for an inline attack upon the substrate phosphorous atom. The PPPases are conserved among species, and many structurally diverse natural toxins co-evolved to target these enzymes.

Conclusion: Although the catalytic site is conserved, opportunities for the development of selective inhibitors of this important group of metalloenzymes exist.

Keywords: Phosphatase, inhibitor, okadaic acid, fostriecin, cantharidin, tautomycin, microcystin crystal structures.

Manning, G.; Whyte, D.B.; Martinez, R.; Hunter, T.; Sudarsanam, S. The protein kinase complement of the human genome. Science, 2002, 298(5600), 1912-1934.
[] [PMID: 12471243]
Milanesi, L.; Petrillo, M.; Sepe, L.; Boccia, A.; D’Agostino, N.; Passamano, M.; Di Nardo, S.; Tasco, G.; Casadio, R.; Paolella, G. Systematic analysis of human kinase genes: A large number of genes and alternative splicing events result in functional and structural diversity. BMC Bioinformatics, 2005, 6(Suppl. 4), S20.
[] [PMID: 16351747]
Anamika, K.; Garnier, N.; Srinivasan, N. Functional diversity of human protein kinase splice variants marks significant expansion of human kinome. BMC Genomics, 2009, 10, 622.
[] [PMID: 20028505]
Sefton, B.M. Overview of protein phosphorylation. Curr. Protoc. Cell Biol. Editor. Board Juan Bonifacino Al,2001, Chapter 14, Unit 14.1.
[] [PMID: 18429113]
Brognard, J.; Hunter, T. Protein kinase signaling networks in cancer. Curr. Opin. Genet. Dev., 2011, 21(1), 4-11.
[] [PMID: 21123047]
Cohen, P. Protein kinases--the major drug targets of the twenty-first century? Nat. Rev. Drug Discov., 2002, 1(4), 309-315.
[] [PMID: 12120282]
Rebelo, S.; Santos, M.; Martins, F. da Cruz e Silva, E.F.; da Cruz e Silva, O.A. Protein phosphatase 1 is a key player in nuclear events. Cell. Signal., 2015, 27(12), 2589-2598.
[] [PMID: 26275498]
Honkanen, R.E.; Golden, T. Regulators of serine/threonine protein phosphatases at the dawn of a clinical era? Curr. Med. Chem., 2002, 9(22), 2055-2075.
[] [PMID: 12369870]
Cohen, P. The origins of protein phosphorylation. Nat. Cell Biol., 2002, 4(5), E127-E130.
[] [PMID: 11988757]
Cohen, P. The regulation of protein function by multisite phosphorylation--a 25year update. Trends Biochem. Sci., 2000, 25(12), 596-601.
[] [PMID: 11116185]
Cohen, P. The role of protein phosphorylation in human health and disease. The Sir Hans Krebs Medal Lecture. Eur. J. Biochem., 2001, 268(19), 5001-5010.
[] [PMID: 11589691]
Ubersax, J.A.; Ferrell, J.E., Jr Mechanisms of specificity in protein phosphorylation. Nat. Rev. Mol. Cell Biol., 2007, 8(7), 530-541.
[] [PMID: 17585314]
de Oliveira, P.S.L.; Ferraz, F.A.N.; Pena, D.A.; Pramio, D.T.; Morais, F.A.; Schechtman, D. Revisiting protein kinase-substrate interactions: Toward therapeutic development. Sci. Signal., 2016, 9(420), re3.
[] [PMID: 27016527]
Kobe, B.; Kampmann, T.; Forwood, J.K.; Listwan, P.; Brinkworth, R.I. Substrate specificity of protein kinases and computational prediction of substrates. Biochim. Biophys. Acta, 2005, 1754(1-2), 200-209.
[] [PMID: 16172032]
Almo, S.C.; Bonanno, J.B.; Sauder, J.M.; Emtage, S.; Dilorenzo, T.P.; Malashkevich, V.; Wasserman, S.R.; Swaminathan, S.; Eswaramoorthy, S.; Agarwal, R.; Kumaran, D.; Madegowda, M.; Ragumani, S.; Patskovsky, Y.; Alvarado, J.; Ramagopal, U.A.; Faber-Barata, J.; Chance, M.R.; Sali, A.; Fiser, A.; Zhang, Z.Y.; Lawrence, D.S.; Burley, S.K. Structural genomics of protein phosphatases. J. Struct. Funct. Genomics, 2007, 8(2-3), 121-140.
[] [PMID: 18058037]
Cohen, P.T. Novel protein serine/threonine phosphatases: Variety is the spice of life. Trends Biochem. Sci., 1997, 22(7), 245-251.
[] [PMID: 9255065]
Alonso, A.; Sasin, J.; Bottini, N.; Friedberg, I.; Friedberg, I.; Osterman, A.; Godzik, A.; Hunter, T.; Dixon, J.; Mustelin, T. Protein tyrosine phosphatases in the human genome. Cell, 2004, 117(6), 699-711.
[] [PMID: 15186772]
Moorhead, G.B.G.; De Wever, V.; Templeton, G.; Kerk, D. Evolution of protein phosphatases in plants and animals. Biochem. J., 2009, 417(2), 401-409.
[] [PMID: 19099538]
Rebay, I. Multiple functions of the eya phosphotyrosine phosphatase. Mol. Cell. Biol., 2015, 36(5), 668-677.
[] [PMID: 26667035]
Barford, D.; Das, A.K.; Egloff, M.P. The structure and mechanism of protein phosphatases: Insights into catalysis and regulation. Annu. Rev. Biophys. Biomol. Struct., 1998, 27, 133-164.
[] [PMID: 9646865]
Jung, S-K.; Jeong, D.G.; Chung, S.J.; Kim, J.H.; Park, B.C.; Tonks, N.K.; Ryu, S.E.; Kim, S.J. Crystal structure of ED-Eya2: Insight into dual roles as a protein tyrosine phosphatase and a transcription factor. FASEB J., 2010, 24(2), 560-569.
[] [PMID: 19858093]
Graves, D.J.; Fischer, E.H.; Krebs, E.G. Specificity studies on muscle phosphorylase phosphatase. J. Biol. Chem., 1960, 235, 805-809.
[PMID: 13829077]
Ingebritsen, T.S.; Cohen, P. The protein phosphatases involved in cellular regulation. 1. Classification and substrate specificities. Eur. J. Biochem., 1983, 132(2), 255-261.
[] [PMID: 6301824]
Shi, Y. Serine/threonine phosphatases: Mechanism through structure. Cell, 2009, 139(3), 468-484.
[] [PMID: 19879837]
Huang, X.; Honkanen, R.E. Molecular cloning, expression, and characterization of a novel human serine/threonine protein phosphatase, PP7, that is homologous to Drosophila retinal degeneration C gene product (rdgC). J. Biol. Chem., 1998, 273(3), 1462-1468.
[] [PMID: 9430683]
Kennelly, P.J. Protein phosphatases--a phylogenetic perspective. Chem. Rev., 2001, 101(8), 2291-2312.
[] [PMID: 11749374]
Ceulemans, H.; Bollen, M. Functional diversity of protein phosphatase-1, a cellular economizer and reset button. Physiol. Rev., 2004, 84(1), 1-39.
[] [PMID: 14715909]
Virshup, D.M.; Shenolikar, S. From promiscuity to precision: Protein phosphatases get a makeover. Mol. Cell, 2009, 33(5), 537-545.
[] [PMID: 19285938]
Chen, M.X.; McPartlin, A.E.; Brown, L.; Chen, Y.H.; Barker, H.M.; Cohen, P.T. A novel human protein serine/threonine phosphatase, which possesses four tetratricopeptide repeat motifs and localizes to the nucleus. EMBO J., 1994, 13(18), 4278-4290.
[] [PMID: 7925273]
Kang, H.; Sayner, S.L.; Gross, K.L.; Russell, L.C.; Chinkers, M. Identification of amino acids in the tetratricopeptide repeat and C-terminal domains of protein phosphatase 5 involved in autoinhibition and lipid activation. Biochemistry, 2001, 40(35), 10485-10490.
[] [PMID: 11523989]
Goldberg, Y. Protein phosphatase 2A: Who shall regulate the regulator? Biochem. Pharmacol., 1999, 57(4), 321-328.
[] [PMID: 9933020]
Janssens, V.; Goris, J. Protein phosphatase 2A: A highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling. Biochem. J., 2001, 353(Pt 3), 417-439.
[] [PMID: 11171037]
Heroes, E.; Lesage, B.; Görnemann, J.; Beullens, M.; Van Meervelt, L.; Bollen, M. The PP1 binding code: A molecular-lego strategy that governs specificity. FEBS J., 2013, 280(2), 584-595.
[] [PMID: 22360570]
Bollen, M.; Peti, W.; Ragusa, M.J.; Beullens, M. The extended PP1 toolkit: Designed to create specificity. Trends Biochem. Sci., 2010, 35(8), 450-458.
[] [PMID: 20399103]
Caenepeel, S.; Charydczak, G.; Sudarsanam, S.; Hunter, T.; Manning, G. The mouse kinome: Discovery and comparative genomics of all mouse protein kinases. Proc. Natl. Acad. Sci. USA, 2004, 101(32), 11707-11712.
[] [PMID: 15289607]
Manning, G.; Plowman, G.D.; Hunter, T.; Sudarsanam, S. Evolution of protein kinase signaling from yeast to man. Trends Biochem. Sci., 2002, 27(10), 514-520.
[] [PMID: 12368087]
Zulawski, M.; Schulze, G.; Braginets, R.; Hartmann, S.; Schulze, W.X. The arabidopsis kinome: phylogeny and evolutionary insights into functional diversification. BMC Genomics, 2014, 15, 548.
[] [PMID: 24984858]
Lesage, B.; Qian, J.; Bollen, M. Spindle checkpoint silencing: PP1 tips the balance. Curr. Biol., 2011, 21(21), R898-R903.
[] [PMID: 22075433]
Barker, H.M.; Craig, S.P.; Spurr, N.K.; Cohen, P.T. Sequence of human protein serine/threonine phosphatase 1 gamma and localization of the gene (PPP1CC) encoding it to chromosome bands 12q24.1-q24.2. Biochim. Biophys. Acta, 1993, 1178(2), 228-233.
[] [PMID: 8394140]
Okano, K.; Heng, H.; Trevisanato, S.; Tyers, M.; Varmuza, S. Genomic organization and functional analysis of the murine protein phosphatase 1c gamma (Ppp1cc) gene. Genomics, 1997, 45(1), 211-215.
[] [PMID: 9339378]
Chakrabarti, R.; Cheng, L.; Puri, P.; Soler, D.; Vijayaraghavan, S. Protein phosphatase PP1 gamma 2 in sperm morphogenesis and epididymal initiation of sperm motility. Asian J. Androl., 2007, 9(4), 445-452.
[] [PMID: 17589781]
Lechward, K.; Awotunde, O.S.; Swiatek, W.; Muszyńska, G. Protein phosphatase 2A: Variety of forms and diversity of functions. Acta Biochim. Pol., 2001, 48(4), 921-933.
[PMID: 11996003]
Van Hoof, C.; Goris, J. Phosphatases in apoptosis: To be or not to be, PP2A is in the heart of the question. Biochim. Biophys. Acta, 2003, 1640(2-3), 97-104.
[] [PMID: 12729918]
Janssens, V.; Zwaenepoel, K.; Rossé, C.; Petit, M.M.R.; Goris, J.; Parker, P.J. PP2A binds to the LIM domains of lipoma-preferred partner through its PR130/B″ subunit to regulate cell adhesion and migration. J. Cell Sci., 2016, 129(8), 1605-1618.
[] [PMID: 26945059]
Chica, N.; Rozalén, A.E.; Pérez-Hidalgo, L.; Rubio, A.; Novak, B.; Moreno, S. Nutritional Control of Cell Size by the Greatwall-Endosulfine-PP2A·B55 Pathway. Curr. Biol., 2016, 26(3), 319-330.
[] [PMID: 26776736]
Seshacharyulu, P.; Pandey, P.; Datta, K.; Batra, S.K. Phosphatase: PP2A structural importance, regulation and its aberrant expression in cancer. Cancer Lett., 2013, 335(1), 9-18.
[] [PMID: 23454242]
Wang, Y.; Xia, Y.; Kuang, D.; Duan, Y.; Wang, G. PP2A regulates SCF-induced cardiac stem cell migration through interaction with p38 MAPK. Life Sci., 2017, 191, 59-67.
[] [PMID: 28986094]
Rusnak, F.; Mertz, P. Calcineurin: Form and function. Physiol. Rev., 2000, 80(4), 1483-1521.
[] [PMID: 11015619]
Musson, R.E.A.; Smit, N.P.M. Regulatory mechanisms of calcineurin phosphatase activity. Curr. Med. Chem., 2011, 18(2), 301-315.
[] [PMID: 21110798]
Nygren, P.J.; Scott, J.D. Regulation of the phosphatase PP2B by protein-protein interactions. Biochem. Soc. Trans., 2016, 44(5), 1313-1319.
[] [PMID: 27911714]
Cohen, P.T.W.; Philp, A.; Vázquez-Martin, C. Protein phosphatase 4--from obscurity to vital functions. FEBS Lett., 2005, 579(15), 3278-3286.
[] [PMID: 15913612]
Voss, M.; Campbell, K.; Saranzewa, N.; Campbell, D.G.; Hastie, C.J.; Peggie, M.W.; Martin-Granados, C.; Prescott, A.R.; Cohen, P.T.W. Protein phosphatase 4 is phosphorylated and inactivated by Cdk in response to spindle toxins and interacts with γ-tubulin. Cell Cycle, 2013, 12(17), 2876-2887.
[] [PMID: 23966160]
Martin-Granados, C.; Philp, A.; Oxenham, S.K.; Prescott, A.R.; Cohen, P.T.W. Depletion of protein phosphatase 4 in human cells reveals essential roles in centrosome maturation, cell migration and the regulation of Rho GTPases. Int. J. Biochem. Cell Biol., 2008, 40(10), 2315-2332.
[] [PMID: 18487071]
Xie, Y.; Jüschke, C.; Esk, C.; Hirotsune, S.; Knoblich, J.A. The phosphatase PP4c controls spindle orientation to maintain proliferative symmetric divisions in the developing neocortex. Neuron, 2013, 79(2), 254-265.
[] [PMID: 23830831]
Oler, A.J.; Cairns, B.R. PP4 dephosphorylates Maf1 to couple multiple stress conditions to RNA polymerase III repression. EMBO J., 2012, 31(6), 1440-1452.
[] [PMID: 22333918]
Hastie, C.J.; Carnegie, G.K.; Morrice, N.; Cohen, P.T. A novel 50 kDa protein forms complexes with protein phosphatase 4 and is located at centrosomal microtubule organizing centres. Biochem. J., 2000, 347(Pt 3), 845-855.
[] [PMID: 10769191]
Gingras, A-C.; Caballero, M.; Zarske, M.; Sanchez, A.; Hazbun, T.R.; Fields, S.; Sonenberg, N.; Hafen, E.; Raught, B.; Aebersold, R. A novel, evolutionarily conserved protein phosphatase complex involved in cisplatin sensitivity. Mol. Cell. Proteomics, 2005, 4(11), 1725-1740.
[] [PMID: 16085932]
Chen, G.I.; Tisayakorn, S.; Jorgensen, C.; D’Ambrosio, L.M.; Goudreault, M.; Gingras, A-C. PP4R4/KIAA1622 forms a novel stable cytosolic complex with phosphoprotein phosphatase 4. J. Biol. Chem., 2008, 283(43), 29273-29284.
[] [PMID: 18715871]
Skarra, D.V.; Goudreault, M.; Choi, H.; Mullin, M.; Nesvizhskii, A.I.; Gingras, A-C.; Honkanen, R.E. Label-free quantitative proteomics and SAINT analysis enable interactome mapping for the human Ser/Thr protein phosphatase 5. Proteomics, 2011, 11(8), 1508-1516.
[] [PMID: 21360678]
Schopf, F.H.; Biebl, M.M.; Buchner, J. The HSP90 chaperone machinery. Nat. Rev. Mol. Cell Biol., 2017, 18(6), 345-360.
[] [PMID: 28429788]
Vaughan, C.K.; Mollapour, M.; Smith, J.R.; Truman, A.; Hu, B.; Good, V.M.; Panaretou, B.; Neckers, L.; Clarke, P.A.; Workman, P.; Piper, P.W.; Prodromou, C.; Pearl, L.H. Hsp90-dependent activation of protein kinases is regulated by chaperone-targeted dephosphorylation of Cdc37. Mol. Cell, 2008, 31(6), 886-895.
[] [PMID: 18922470]
Oberoi, J.; Dunn, D.M.; Woodford, M.R.; Mariotti, L.; Schulman, J.; Bourboulia, D.; Mollapour, M.; Vaughan, C.K. Structural and functional basis of protein phosphatase 5 substrate specificity. Proc. Natl. Acad. Sci. USA, 2016, 113(32), 9009-9014.
[] [PMID: 27466404]
Shao, J.; Hartson, S.D.; Matts, R.L. Evidence that protein phosphatase 5 functions to negatively modulate the maturation of the Hsp90-dependent heme-regulated eIF2alpha kinase. Biochemistry, 2002, 41(21), 6770-6779.
[] [PMID: 12022881]
Golden, T.; Swingle, M.; Honkanen, R.E. The role of serine/threonine protein phosphatase type 5 (PP5) in the regulation of stress-induced signaling networks and cancer. Cancer Metastasis Rev., 2008, 27(2), 169-178.
[] [PMID: 18253812]
Zhou, G.; Golden, T.; Aragon, I.V.; Honkanen, R.E. Ser/Thr protein phosphatase 5 inactivates hypoxia-induced activation of an apoptosis signal-regulating kinase 1/MKK-4/JNK signaling cascade. J. Biol. Chem., 2004, 279(45), 46595-46605.
[] [PMID: 15328343]
Urban, G.; Golden, T.; Aragon, I.V.; Scammell, J.G.; Dean, N.M.; Honkanen, R.E. Identification of an estrogen-inducible phosphatase (PP5) that converts MCF-7 human breast carcinoma cells into an estrogen-independent phenotype when expressed constitutively. J. Biol. Chem., 2001, 276(29), 27638-27646.
[] [PMID: 11331294]
Zhang, Y.; Leung, D.Y.M.; Nordeen, S.K.; Goleva, E. Estrogen inhibits glucocorticoid action via protein phosphatase 5 (PP5)-mediated glucocorticoid receptor dephosphorylation. J. Biol. Chem., 2009, 284(36) 24542- 2[h4t5tp5:2//.d] [PMID: 19586900]
Swingle, M.R.; Honkanen, R.E.; Ciszak, E.M. Structural basis for the catalytic activity of human serine/threonine protein phosphatase-5. J. Biol. Chem., 2004, 279(32), 33992-33999.
[] [PMID: 15155720]
Yang, J.; Roe, S.M.; Cliff, M.J.; Williams, M.A.; Ladbury, J.E.; Cohen, P.T.W.; Barford, D. Molecular basis for TPR domain-mediated regulation of protein phosphatase 5. EMBO J., 2005, 24(1), 1-10.
[] [PMID: 15577939]
Chen, M.X.; Cohen, P.T. Activation of protein phosphatase 5 by limited proteolysis or the binding of polyunsaturated fatty acids to the TPR domain. FEBS Lett., 1997, 400(1), 136-140.
[] [PMID: 9000529]
Sinclair, C.; Borchers, C.; Parker, C.; Tomer, K.; Charbonneau, H.; Rossie, S. The tetratricopeptide repeat domain and a C-terminal region control the activity of Ser/Thr protein phosphatase 5. J. Biol. Chem., 1999, 274(33), 23666-23672.
[] [PMID: 10438550]
Skinner, J.; Sinclair, C.; Romeo, C.; Armstrong, D.; Charbonneau, H.; Rossie, S. Purification of a fatty acid-stimulated protein-serine/threonine phosphatase from bovine brain and its identification as a homolog of protein phosphatase 5. J. Biol. Chem., 1997, 272(36), 22464-22471.
[] [PMID: 9278397]
Ramsey, A.J.; Chinkers, M. Identification of potential physiological activators of protein phosphatase 5. Biochemistry, 2002, 41(17), 5625-5632.
[] [PMID: 11969423]
Rusin, S.F.; Schlosser, K.A.; Adamo, M.E.; Kettenbach, A.N. Quantitative phosphoproteomics reveals new roles for the protein phosphatase PP6 in mitotic cells. Sci. Signal., 2015, 8(398), rs12.
[] [PMID: 26462736]
Zeng, K.; Bastos, R.N.; Barr, F.A.; Gruneberg, U. Protein phosphatase 6 regulates mitotic spindle formation by controlling the T-loop phosphorylation state of Aurora A bound to its activator TPX2. J. Cell Biol., 2010, 191(7), 1315-1332.
[] [PMID: 21187329]
Hu, M.W.; Wang, Z.B.; Teng, Y.; Jiang, Z.Z.; Ma, X.S.; Hou, N.; Cheng, X.; Schatten, H.; Xu, X.; Yang, X.; Sun, Q.Y. Loss of protein phosphatase 6 in oocytes causes failure of meiosis II exit and impaired female fertility. J. Cell Sci., 2015, 128(20), 3769-3780.
[] [PMID: 26349807]
Ziembik, M.A.; Bender, T.P.; Larner, J.M.; Brautigan, D.L. Functions of protein phosphatase-6 in NF-κB signaling and in lymphocytes. Biochem. Soc. Trans., 2017, 45(3), 693-701.
[] [PMID: 28620030]
Wengrod, J.; Wang, D.; Weiss, S.; Zhong, H.; Osman, I.; Gardner, L.B. Phosphorylation of eIF2α triggered by mTORC1 inhibition and PP6C activation is required for autophagy and is aberrant in PP6C-mutated melanoma. Sci. Signal., 2015, 8(367), ra27.
[] [PMID: 25759478]
Ye, J.; Shi, H.; Shen, Y.; Peng, C.; Liu, Y.; Li, C.; Deng, K.; Geng, J.; Xu, T.; Zhuang, Y.; Zheng, B.; Tao, W. PP6 controls T cell development and homeostasis by negatively regulating distal TCR signaling. J. Immunol., 2015, 194(4), 1654-1664.
[] [PMID: 25609840]
Hammond, D.; Zeng, K.; Espert, A.; Bastos, R.N.; Baron, R.D.; Gruneberg, U.; Barr, F.A. Melanoma-associated mutations in protein phosphatase 6 cause chromosome instability and DNA damage owing to dysregulated Aurora-A. J. Cell Sci., 2013, 126(Pt 15), 3429-3440.
[] [PMID: 23729733]
Stefansson, B.; Brautigan, D.L. Protein phosphatase 6 subunit with conserved Sit4-associated protein domain targets IkappaBepsilon. J. Biol. Chem., 2006, 281(32), 22624-22634.
[] [PMID: 16769727]
Stefansson, B.; Ohama, T.; Daugherty, A.E.; Brautigan, D.L. Protein phosphatase 6 regulatory subunits composed of ankyrin repeat domains. Biochemistry, 2008, 47(5), 1442-1451.
[] [PMID: 18186651]
Andreeva, A.V.; Kutuzov, M.A. PPEF/PP7 protein Ser/Thr phosphatases. Cell. Mol. Life Sci., 2009, 66(19), 3103-3110.
[] [PMID: 19662497]
Peti, W.; Nairn, A.C.; Page, R. Structural basis for protein phosphatase 1 regulation and specificity. FEBS J., 2013, 280(2), 596-611.
[] [PMID: 22284538]
Verbinnen, I.; Ferreira, M.; Bollen, M. Biogenesis and activity regulation of protein phosphatase 1. Biochem. Soc. Trans., 2017, 45(1), 89-99.
[] [PMID: 28202662]
Xu, Y.; Xing, Y.; Chen, Y.; Chao, Y.; Lin, Z.; Fan, E.; Yu, J.W.; Strack, S.; Jeffrey, P.D.; Shi, Y. Structure of the protein phosphatase 2A holoenzyme. Cell, 2006, 127(6), 1239-1251.
[] [PMID: 17174897]
Chattopadhyay, D.; Swingle, M.R.; Salter, E.A.; Wood, E.; D’Arcy, B.; Zivanov, C.; Abney, K.; Musiyenko, A.; Rusin, S.F.; Kettenbach, A.; Yet, L.; Schroeder, C.E.; Golden, J.E.; Dunham, W.H.; Gingras, A-C.; Banerjee, S.; Forbes, D.; Wierzbicki, A.; Honkanen, R.E. Crystal structures and mutagenesis of PPP-family ser/thr protein phosphatases elucidate the selectivity of cantharidin and novel norcantharidin-based inhibitors of PP5C. Biochem. Pharmacol., 2016, 109, 14-26.
[] [PMID: 27002182]
Bertini, I.; Calderone, V.; Fragai, M.; Luchinat, C.; Talluri, E. Structural basis of serine/threonine phosphatase inhibition by the archetypal small molecules cantharidin and norcantharidin. J. Med. Chem., 2009, 52(15), 4838-4843.
[] [PMID: 19601647]
Lad, C.; Williams, N.H.; Wolfenden, R. The rate of hydrolysis of phosphomonoester dianions and the exceptional catalytic proficiencies of protein and inositol phosphatases. Proc. Natl. Acad. Sci. USA, 2003, 100(10), 5607-5610.
[] [PMID: 12721374]
Zhang, J.; Zhang, Z.; Brew, K.; Lee, E.Y. Mutational analysis of the catalytic subunit of muscle protein phosphatase-1. Biochemistry, 1996, 35(20), 6276-6282.
[] [PMID: 8639569]
Zhang, L.; Lee, E.Y. Mutational analysis of substrate recognition by protein phosphatase 1. Biochemistry, 1997, 36(27), 8209-8214.
[] [PMID: 9204865]
Martin, B.L.; Jurado, L.A.; Hengge, A.C. Comparison of the reaction progress of calcineurin with Mn2+ and Mg2+. Biochemistry, 1999, 38(11), 3386-3392.
[] [PMID: 10079083]
Egloff, M.P.; Cohen, P.T.; Reinemer, P.; Barford, D. Crystal structure of the catalytic subunit of human protein phosphatase 1 and its complex with tungstate. J. Mol. Biol., 1995, 254(5), 942-959.
[] [PMID: 7500362]
Xing, Y.; Xu, Y.; Chen, Y.; Jeffrey, P.D.; Chao, Y.; Lin, Z.; Li, Z.; Strack, S.; Stock, J.B.; Shi, Y. Structure of protein phosphatase 2A core enzyme bound to tumor-inducing toxins. Cell, 2006, 127(2), 341-353.
[] [PMID: 17055435]
Heroes, E.; Rip, J.; Beullens, M.; Van Meervelt, L.; De Gendt, S.; Bollen, M. Metals in the active site of native protein phosphatase-1. J. Inorg. Biochem., 2015, 149, 1-5.
[] [PMID: 25890482]
Namgaladze, D.; Hofer, H.W.; Ullrich, V. Redox control of calcineurin by targeting the binuclear Fe(2+)-Zn(2+) center at the enzyme active site. J. Biol. Chem., 2002, 277(8), 5962-5969.
[] [PMID: 11741966]
Nishito, Y.; Usui, H.; Shinzawa-Itoh, K.; Inoue, R.; Tanabe, O.; Nagase, T.; Murakami, T.; Takeda, M. Direct metal analyses of Mn2+-dependent and -independent protein phosphatase 2A from human erythrocytes detect zinc and iron only in the Mn2+-independent one. FEBS Lett., 1999, 447(1), 29-33.
[] [PMID: 10218576]
King, M.M.; Huang, C.Y. The calmodulin-dependent activation and deactivation of the phosphoprotein phosphatase, calcineurin, and the effect of nucleotides, pyrophosphate, and divalent metal ions. Identification of calcineurin as a Zn and Fe metalloenzyme. J. Biol. Chem., 1984, 259(14), 8847-8856.
[PMID: 6086614]
Martin, B.L.; Graves, D.J. Mechanistic aspects of the low-molecular-weight phosphatase activity of the calmodulin-activated phosphatase, calcineurin. J. Biol. Chem., 1986, 261(31), 14545-14550.
[PMID: 3771542]
Hengge, A.C.; Martin, B.L. Isotope effect studies on the calcineurin phosphoryl-transfer reaction: Transition state structure and effect of calmodulin and Mn2+. Biochemistry, 1997, 36(33), 10185-10191.
[] [PMID: 9254616]
Mondragon, A.; Griffith, E.C.; Sun, L.; Xiong, F.; Armstrong, C.; Liu, J.O. Overexpression and purification of human calcineurin alpha from Escherichia coli and assessment of catalytic functions of residues surrounding the binuclear metal center. Biochemistry, 1997, 36(16), 4934-4942.
[] [PMID: 9125515]
Martin, B.; Pallen, C.J.; Wang, J.H.; Graves, D.J. Use of fluorinated tyrosine phosphates to probe the substrate specificity of the low molecular weight phosphatase activity of calcineurin. J. Biol. Chem., 1985, 260(28), 14932-14937.
[PMID: 2415511]
Jackson, M.D.; Denu, J.M. Molecular reactions of protein phosphatases--insights from structure and chemistry. Chem. Rev., 2001, 101(8), 2313-2340.
[] [PMID: 11749375]
Bertini, I.; Luchinat, C. The reaction pathways of zinc enzymes and related biological catalysts. Bioinorg. Chem., Bertini, I.; Gray, H.B.; Lippard, S.J; Valentine, J.S., Ed.; University Science: California, 1994, pp. 37-106.
Bertini, I.; Luchinat, C.; Rosi, M.; Sgamellotti, A.; Tarantelli, F. pKa of zinc-bound water and nucleophilicity of hydroxo-containing species. ab initio calculations on models for zinc enzymes. Inorg. Chem., 1990, 29, 1460-1463.
Mesecar, A.D.; Stoddard, B.L.; Koshland, D.E., Jr Orbital steering in the catalytic power of enzymes: Small structural changes with large catalytic consequences. Science, 1997, 277(5323), 202-206.
[] [PMID: 9211842]
Hoff, R.H.; Mertz, P.; Rusnak, F.; Hengge, A.C. The transition state of the phosphoryl-transfer reaction catalyzed by the lambda ser/thr protein phosphatase. J. Am. Chem. Soc., 1999, 121, 6382-6390.
Rowlett, R.S.; Silverman, D.N. Kinetics of the protonation of buffer and hydration of carbon dioxide catalyzed by human carbonic anhydrase II. J. Am. Chem. Soc., 1982, 104, 6737-6741.
Azzi, J.R.; Sayegh, M.H.; Mallat, S.G. Calcineurin inhibitors: 40 years later, can’t live without..... J. Immunol., 2013, 191(12), 5785-5791.
[] [PMID: 24319282]
Barik, S. Immunophilins: For the love of proteins. Cell. Mol. Life Sci., 2006, 63(24), 2889-2900.
[] [PMID: 17075696]
Harikishore, A.; Yoon, H.S. Immunophilins: Structures, mechanisms and ligands. Curr. Mol. Pharmacol., 2015, 9(1), 37-47.
[] [PMID: 25986569]
Grigoriu, S.; Bond, R.; Cossio, P.; Chen, J.A.; Ly, N.; Hummer, G.; Page, R.; Cyert, M.S.; Peti, W. The molecular mechanism of substrate engagement and immunosuppressant inhibition of calcineurin. PLoS Biol., 2013, 11(2)e1001492
[] [PMID: 23468591]
Kissinger, C.R.; Parge, H.E.; Knighton, D.R.; Lewis, C.T.; Pelletier, L.A.; Tempczyk, A.; Kalish, V.J.; Tucker, K.D.; Showalter, R.E.; Moomaw, E.W. Crystal structures of human calcineurin and the human FKBP12-FK506-calcineurin complex. Nature, 1995, 378(6557), 641-644.
[] [PMID: 8524402]
Griffith, J.P.; Kim, J.L.; Kim, E.E.; Sintchak, M.D.; Thomson, J.A.; Fitzgibbon, M.J.; Fleming, M.A.; Caron, P.R.; Hsiao, K.; Navia, M.A. X-ray structure of calcineurin inhibited by the immunophilin-immunosuppressant FKBP12-FK506 complex. Cell, 1995, 82(3), 507-522.
[] [PMID: 7543369]
Ke, H.; Huai, Q. Structures of calcineurin and its complexes with immunophilins-immunosuppressants. Biochem. Biophys. Res. Commun., 2003, 311(4), 1095-1102.
[] [PMID: 14623295]
Huai, Q.; Kim, H.Y.; Liu, Y.; Zhao, Y.; Mondragon, A.; Liu, J.O.; Ke, H. Crystal structure of calcineurin-cyclophilin-cyclosporin shows common but distinct recognition of immunophilin-drug complexes. Proc. Natl. Acad. Sci. USA, 2002, 99(19), 12037-12042.
[] [PMID: 12218175]
Takai, A.; Bialojan, C.; Troschka, M.; Rüegg, J.C. Smooth muscle myosin phosphatase inhibition and force enhancement by black sponge toxin. FEBS Lett., 1987, 217(1), 81-84.
[] [PMID: 3036577]
Honkanen, R.E.; Zwiller, J.; Moore, R.E.; Daily, S.L.; Khatra, B.S.; Dukelow, M.; Boynton, A.L. Characterization of microcystin-LR, a potent inhibitor of type 1 and type 2A protein phosphatases. J. Biol. Chem., 1990, 265(32), 19401-19404.
[PMID: 2174036]
Honkanen, R.E.; Dukelow, M.; Zwiller, J.; Moore, R.E.; Khatra, B.S.; Boynton, A.L. Cyanobacterial nodularin is a potent inhibitor of type 1 and type 2A protein phosphatases. Mol. Pharmacol., 1991, 40(4), 577-583.
[PMID: 1656193]
Suganuma, M.; Fujiki, H.; Furuya-Suguri, H.; Yoshizawa, S.; Yasumoto, S.; Kato, Y.; Fusetani, N.; Sugimura, T. Calyculin A, an inhibitor of protein phosphatases, a potent tumor promoter on CD-1 mouse skin. Cancer Res., 1990, 50(12), 3521-3525.
[PMID: 2160320]
Ishihara, H.; Martin, B.L.; Brautigan, D.L.; Karaki, H.; Ozaki, H.; Kato, Y.; Fusetani, N.; Watabe, S.; Hashimoto, K.; Uemura, D. Calyculin A and okadaic acid: Inhibitors of protein phosphatase activity. Biochem. Biophys. Res. Commun., 1989, 159(3), 871-877.
[] [PMID: 2539153]
Capon, R.J.; Rooney, F.; Murray, L.M.; Collins, E.; Sim, A.T.R.; Rostas, J.A.P.; Butler, M.S.; Carroll, A.R. Dragmacidins: New protein phosphatase inhibitors from a southern australian deep-water marine sponge, Spongosorites sp. J. Nat. Prod., 1998, 61(5), 660-662.
[] [PMID: 9599272]
Matsuzawa, S.; Suzuki, T.; Suzuki, M.; Matsuda, A.; Kawamura, T.; Mizuno, Y.; Kikuchi, K. Thyrsiferyl 23-acetate is a novel specific inhibitor of protein phosphatase PP2A. FEBS Lett., 1994, 356(2-3), 272-274.
[] [PMID: 7805852]
Mamber, S.W.; Okasinski, W.G.; Pinter, C.D.; Tunac, J.B. Antimycotic effects of the novel antitumor agents fostriecin (CI-920), PD 113,270 and PD 113,271. J. Antibiot. (Tokyo), 1986, 39(10), 1467-1472.
[] [PMID: 3781915]
Burke, C.P.; Haq, N.; Boger, D.L. Total synthesis, assignment of the relative and absolute stereochemistry, and structural reassignment of phostriecin (aka Sultriecin). J. Am. Chem. Soc., 2010, 132(7), 2157-2159.
[] [PMID: 20108904]
Ohkuma, H.; Naruse, N.; Nishiyama, Y.; Tsuno, T.; Hoshino, Y.; Sawada, Y.; Konishi, M.; Oki, T. Sultriecin, a new antifungal and antitumor antibiotic from Streptomyces roseiscleroticus. Production, isolation, structure and biological activity. J. Antibiot. (Tokyo), 1992, 45(8), 1239-1249.
[] [PMID: 1399844]
Lawhorn, B.G.; Boga, S.B.; Wolkenberg, S.E.; Colby, D.A.; Gauss, C-M.; Swingle, M.R.; Amable, L.; Honkanen, R.E.; Boger, D.L. Total synthesis and evaluation of cytostatin, its C10-C11 diastereomers, and additional key analogues: Impact on PP2A inhibition. J. Am. Chem. Soc., 2006, 128(51), 16720-16732.
[] [PMID: 17177422]
Ozasa, T.; Tanaka, K.; Sasamata, M.; Kaniwa, H.; Shimizu, M.; Matsumoto, H.; Iwanami, M. Novel antitumor antibiotic phospholine. 2. Structure determination. J. Antibiot. (Tokyo), 1989, 42(9), 1339-1343.
[] [PMID: 2793587]
Kohama, T.; Enokita, R.; Okazaki, T.; Miyaoka, H.; Torikata, A.; Inukai, M.; Kaneko, I.; Kagasaki, T.; Sakaida, Y.; Satoh, A. Novel microbial metabolites of the phoslactomycins family induce production of colony-stimulating factors by bone marrow stromal cells. I. Taxonomy, fermentation and biological properties. J. Antibiot. (Tokyo), 1993, 46(10), 1503-1511.
[] [PMID: 7503975]
Fushimi, S.; Nishikawa, S.; Shimazu, A.; Seto, H. Studies on new phosphate ester antifungal antibiotics phoslactomycins. I. Taxonomy, fermentation, purification and biological activities. J. Antibiot. (Tokyo), 1989, 42(7), 1019-1025.
[] [PMID: 2753808]
Hori, M.; Magae, J.; Han, Y.G.; Hartshorne, D.J.; Karaki, H. A novel protein phosphatase inhibitor, tautomycin. Effect on smooth muscle. FEBS Lett., 1991, 285(1), 145-148.
[] [PMID: 1648511]
Cheng, X.C.; Kihara, T.; Ying, X.; Uramoto, M.; Osada, H.; Kusakabe, H.; Wang, B.N.; Kobayashi, Y.; Ko, K.; Yamaguchi, I. A new antibiotic, tautomycetin. J. Antibiot. (Tokyo), 1989, 42(1), 141-144.
[] [PMID: 2921220]
Honkanen, R.E. Cantharidin, another natural toxin that inhibits the activity of serine/threonine protein phosphatases types 1 and 2A. FEBS Lett., 1993, 330(3), 283-286.
[] [PMID: 8397101]
Dawson, R.M. The toxicology of microcystins. Toxicon, 1998, 36(7), 953-962.
[] [PMID: 9690788]
Bishop, C.T.; Anet, E.F.; Gorham, P.R. Isolation and identification of the fast-death factor in Microcystis aeruginosa NRC-1. Can. J. Biochem. Physiol., 1959, 37(3), 453-471.
[] [PMID: 13638864]
Konst, H.; McKercher, P.D.; Gorham, P.R.; Robertson, A.; Howell, J. Symptoms and pathology produced by toxic Microcystis aeruginosa NRC-1 in laboratory and domestic animals. Can. J. Comp. Med. Vet. Sci., 1965, 29(9), 221-228.
[PMID: 4221987]
Fischer, W.J.; Altheimer, S.; Cattori, V.; Meier, P.J.; Dietrich, D.R.; Hagenbuch, B. Organic anion transporting polypeptides expressed in liver and brain mediate uptake of microcystin. Toxicol. Appl. Pharmacol., 2005, 203(3), 257-263.
[] [PMID: 15737679]
Hastie, C.J.; Cohen, P.T. Purification of protein phosphatase 4 catalytic subunit: Inhibition by the antitumour drug fostriecin and other tumour suppressors and promoters. FEBS Lett., 1998, 431(3), 357-361.
[] [PMID: 9714542]
Swingle, M.; Ni, L.; Honkanen, R.E. Small-molecule inhibitors of ser/thr protein phosphatases: Specificity, use and common forms of abuse. Methods Mol. Biol., 2007, 365, 23-38.
[PMID: 17200551]
Prickett, T.D.; Brautigan, D.L. The alpha4 regulatory subunit exerts opposing allosteric effects on protein phosphatases PP6 and PP2A. J. Biol. Chem., 2006, 281(41), 30503-30511.
[] [PMID: 16895907]
MacKintosh, C.; Beattie, K.A.; Klumpp, S.; Cohen, P.; Codd, G.A. Cyanobacterial microcystin-LR is a potent and specific inhibitor of protein phosphatases 1 and 2A from both mammals and higher plants. FEBS Lett., 1990, 264(2), 187-192.
[] [PMID: 2162782]
Goldberg, J.; Huang, H.B.; Kwon, Y.G.; Greengard, P.; Nairn, A.C.; Kuriyan, J. Three-dimensional structure of the catalytic subunit of protein serine/threonine phosphatase-1. Nature, 1995, 376(6543), 745-753.
[] [PMID: 7651533]
Maynes, J.T.; Bateman, K.S.; Cherney, M.M.; Das, A.K.; Luu, H.A.; Holmes, C.F.B.; James, M.N.G. Crystal structure of the tumor-promoter okadaic acid bound to protein phosphatase-1. J. Biol. Chem., 2001, 276(47), 44078-44082.
[] [PMID: 11535607]
Valdiglesias, V.; Prego-Faraldo, M.V.; Pásaro, E.; Méndez, J.; Laffon, B. Okadaic acid: More than a diarrheic toxin. Mar. Drugs, 2013, 11(11), 4328-4349.
[] [PMID: 24184795]
Prego-Faraldo, M.V.; Valdiglesias, V.; Méndez, J.; Eirín-López, J.M. Okadaic acid meet and greet: An insight into detection methods, response strategies and genotoxic effects in marine invertebrates. Mar. Drugs, 2013, 11(8), 2829-2845.
[] [PMID: 23939476]
Bialojan, C.; Takai, A. Inhibitory effect of a marine-sponge toxin, okadaic acid, on protein phosphatases. Specificity and kinetics. Biochem. J., 1988, 256(1), 283-290.
[] [PMID: 2851982]
Ni, L.; Swingle, M.S.; Bourgeois, A.C.; Honkanen, R.E. High yield expression of serine/threonine protein phosphatase type 5, and a fluorescent assay suitable for use in the detection of catalytic inhibitors. Assay Drug Dev. Technol., 2007, 5(5), 645-653.
[] [PMID: 17939754]
Zhang, L.; Zhang, Z.; Long, F.; Lee, E.Y. Tyrosine-272 is involved in the inhibition of protein phosphatase-1 by multiple toxins. Biochemistry, 1996, 35(5), 1606-1611.
[] [PMID: 8634292]
MacKintosh, C.; Klumpp, S. Tautomycin from the bacterium Streptomyces verticillatus. Another potent and specific inhibitor of protein phosphatases 1 and 2A. FEBS Lett., 1990, 277(1-2), 137-140.
[] [PMID: 2176611]
Honkanen, R.E.; Codispoti, B.A.; Tse, K.; Boynton, A.L.; Honkanan, R.E. Characterization of natural toxins with inhibitory activity against serine/threonine protein phosphatases. Toxicon, 1994, 32(3), 339-350.
[] [PMID: 8016855]
Kelker, M.S.; Page, R.; Peti, W. Crystal structures of protein phosphatase-1 bound to nodularin-R and tautomycin: A novel scaffold for structure-based drug design of serine/threonine phosphatase inhibitors. J. Mol. Biol., 2009, 385(1), 11-21.
[] [PMID: 18992256]
Wakimoto, T.; Matsunaga, S.; Takai, A.; Fusetani, N. Insight into binding of calyculin A to protein phosphatase 1: Isolation of hemicalyculin a and chemical transformation of calyculin A. Chem. Biol., 2002, 9(3), 309-319.
[] [PMID: 11927256]
Kita, A.; Matsunaga, S.; Takai, A.; Kataiwa, H.; Wakimoto, T.; Fusetani, N.; Isobe, M.; Miki, K. Crystal structure of the complex between calyculin A and the catalytic subunit of protein phosphatase 1. Structure, 2002, 10(5), 715-724.
[] [PMID: 12015153]
Lê, L.H.; Erlichman, C.; Pillon, L.; Thiessen, J.J.; Day, A.; Wainman, N.; Eisenhauer, E.A.; Moore, M.J. Phase I and pharmacokinetic study of fostriecin given as an intravenous bolus daily for five consecutive days. Invest. New Drugs, 2004, 22(2), 159-167.
[] [PMID: 14739664]
Jackson, R.C.; Fry, D.W.; Boritzki, T.J.; Roberts, B.J.; Hook, K.E.; Leopold, W.R. The biochemical pharmacology of CI-920, a structurally novel antibiotic with antileukemic activity. Adv. Enzyme Regul., 1985, 23, 193-215.
[] [PMID: 3840949]
Leopold, W.R.; Shillis, J.L.; Mertus, A.E.; Nelson, J.M.; Roberts, B.J.; Jackson, R.C. Anticancer activity of the structurally novel antibiotic Cl-920 and its analogues. Cancer Res., 1984, 44(5), 1928-1932.
[PMID: 6546897]
Walsh, A.H.; Cheng, A.; Honkanen, R.E. Fostriecin, an antitumor antibiotic with inhibitory activity against serine/threonine protein phosphatases types 1 (PP1) and 2A (PP2A), is highly selective for PP2A. FEBS Lett., 1997, 416(3), 230-234.
[] [PMID: 9373158]
Swingle, M.R.; Amable, L.; Lawhorn, B.G.; Buck, S.B.; Burke, C.P.; Ratti, P.; Fischer, K.L.; Boger, D.L.; Honkanen, R.E. Structure-activity relationship studies of fostriecin, cytostatin, and key analogs, with PP1, PP2A, PP5, and(beta12-beta13)-chimeras (PP1/PP2A and PP5/PP2A), provide further insight into the inhibitory actions of fostriecin family inhibitors. J. Pharmacol. Exp. Ther., 2009, 331(1), 45-53.
[] [PMID: 19592665]
Buck, S.B.; Hardouin, C.; Ichikawa, S.; Soenen, D.R.; Gauss, C-M.; Hwang, I.; Swingle, M.R.; Bonness, K.M.; Honkanen, R.E.; Boger, D.L. Fundamental role of the fostriecin unsaturated lactone and implications for selective protein phosphatase inhibition. J. Am. Chem. Soc., 2003, 125(51), 15694-15695.
[] [PMID: 14677930]
Takeuchi, T.; Takahashi, N.; Ishi, K.; Kusayanagi, T.; Kuramochi, K.; Sugawara, F. Antitumor antibiotic fostriecin covalently binds to cysteine-269 residue of protein phosphatase 2A catalytic subunit in mammalian cells. Bioorg. Med. Chem., 2009, 17(23), 8113-8122.
[] [PMID: 19857968]
Evans, D.R.; Simon, J.A. The predicted beta12-beta13 loop is important for inhibition of PP2Acalpha by the antitumor drug fostriecin. FEBS Lett., 2001, 498(1), 110-115.
[] [PMID: 11389908]
Moed, L.; Shwayder, T.A.; Chang, M.W. Cantharidin revisited: A blistering defense of an ancient medicine. Arch. Dermatol., 2001, 137(10), 1357-1360.
[] [PMID: 11594862]
Wang, G.S. Medical uses of mylabris in ancient China and recent studies. J. Ethnopharmacol., 1989, 26(2), 147-162.
[] [PMID: 2689797]
Liao, Y.F.; Wang, Y.; Huang, Y.; Zha, S.F.; Liu, J.J.; Wang, Z.K.; Yin, Y.P.; Liao, Y.F.; Wang, Y. isolation and functional analysis of mcmena, a gene encoding a 1,4-dihydroxy-2-naphthoate octaprenyltransferase in mylabris cichorii. Arch. Insect Biochem. Physiol., 2015, 89(3), 127-137.
[] [PMID: 25772016]
Oaks, W.W.; Ditunno, J.F.; Magnani, T.; Levy, H.A.; Mills, L.C. Cantharidin poisoning. Arch. Intern. Med., 1960, 105, 574-582.
[] [PMID: 14428136]
Al-Dawsari, N.A.; Masterpol, K.S. Cantharidin in Dermatology. Skinmed, 2016, 14(2), 111-114.
[PMID: 27319954]
Prickett, T.D.; Brautigan, D.L. The α4 regulatory subunit exerts opposing allosteric effects on protein phosphatases PP6 and PP2A. J. Biol. Chem., 2006, 281(41), 30503-30511.
[] [PMID: 16895907]
Li, Y.M.; Mackintosh, C.; Casida, J.E. Protein phosphatase 2A and its [3H]cantharidin/[3H]endothall thioanhydride binding site. Inhibitor specificity of cantharidin and ATP analogues. Biochem. Pharmacol., 1993, 46(8), 1435-1443.
[] [PMID: 8240393]
Swingle, M.R.; Honkanen, R.E. Development and validation of a robust and sensitive assay for the discovery of selective inhibitors for serine/threonine protein phosphatases PP1α (PPP1C) and PP5 (PPP5C). Assay Drug Dev. Technol., 2014, 12(8), 481-496.
[] [PMID: 25383722]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Published on: 07 May, 2018
Page: [2634 - 2660]
Pages: 27
DOI: 10.2174/0929867325666180508095242
Price: $65

Article Metrics

PDF: 52
HTML: 11