Cationic porphyrins are tunable gatekeepers of the 20S proteasome(473 visite)(PDF privato147 visite) Santoro AM, Cunsolo A, D'Urso A, Sbardella D, Tundo GR, Ciaccio C, Coletta M, Diana D, Fattorusso R, Persico M, Di Dato A, Fattorusso C, Milardi D, Purrello R
*** IBB - CNR *** Istituto di Biostrutture e Bioimmagini – CNR UOS di Catania, Via P. Gaifami 18, 95126 Catania, Italy. Dipartimento di Scienze Chimiche, Università di Catania, Viale Andrea Doria 6, 95125 Catania, Italy. Dipartimento di Farmacia Università di Napoli “Federico II”, Via D. Montesano, 49 I-80131 Napoli, Italy.
S. Murata, H. Yashiroda and K. Tanaka, Nat. Rev. Mol. Cell Biol., 2009, 10, 104 CrossRefCASPubMed.
N. Gallastegui and M. Groll, Trends Biochem. Sci., 2010, 35, 634 CrossRefCASPubMed.
O. Coux, K. Tanaka and A. L. Goldberg, Annu. Rev. Biochem., 1996, 65, 801 CrossRefCASPubMed.
W. Baumeister, J. Walz, F. Zühl and E. Seemüller, Cell, 1998, 92, 367 CrossRefCASPubMed.
M. H. Glickman, D. M. Rubin, O. Coux, I. Wefes, G. Pfeifer, Z. Cjeka, W. Baumeister, V. A. Fried and D. Finley, Cell, 1998, 94(5), 6156 CrossRef.
C. S. Arendt and M. Hochstrasser, Proc. Natl. Acad. Sci. U. S. A., 1997, 94, 7156 CrossRefCAS.
W. Heinemeyer, M. Fischer, T. Krimmer, U. Stachon and D. H. Wolf, J. Biol. Chem., 1997, 272, 25200 CrossRefCASPubMed.
A. F. Kisselev, A. Callard and A. L. Goldberg, J. Biol. Chem., 2006, 281, 8582 CrossRefCASPubMed.
M. Groll, L. Ditzel, J. Löwe, D. Stock, M. Bochtler, H. D. Bartunik and R. Huber, Nature, 1997, 386, 463 CrossRefCASPubMed.
M. Groll, M. Bajorek, A. Kohler, L. Moroder, D. M. Rubin, R. Huber, M. Glickman and D. Finley, Nat. Struct. Biol., 2000, 7, 1062 CrossRefCASPubMed.
M. Groll and R. Huber, Int. J. Biochem. Cell Biol., 2003, 5, 606 CrossRef.
A. Kohler, M. Bajorek, M. Groll, L. Moroder, D. M. Rubin, R. Huber, M. Glickman and D. Finley, Biochimie, 2001, 83, 325 CrossRefCASPubMed.
D. J. McConkey and K. Zhu, Drug Resist. Updates, 2008, 11, 164 CrossRefCASPubMed.
A. Lehmann, K. Jechow and C. Enenkel, EMBO Rep., 2008, 9(12), 1237 CrossRefCASPubMed.
G. Ben-Nissan and M. Sharon, Biomolecules, 2014, 4, 862 CrossRefCASPubMed.
E. A. Obeng, L. M. Carlson, D. M. Gutman, W. J. Harrington Jr, K. P. Lee and L. H. Boise, Blood, 2006, 107(12), 4907 CrossRefCASPubMed.
S. T. Nawrocki, J. S. Carew, K. Dunner Jr, L. H. Boise, P. J. Chiao, P. Huang, J. L. Abbruzzese and D. J. McConkey, Cancer Res., 2005, 65(24), 11510 CrossRefCASPubMed.
G. Bianchi, L. Oliva, P. Cascio, N. Pengo, F. Fontana, F. Cerruti, A. Orsi, E. Pasqualetto, A. Mezghrani, V. Calbi, G. Palladini, N. Giuliani, K. C. Anderson, R. Sitia and S. Cenci, Blood, 2009, 13(13), 3040 CrossRefPubMed.
L. R. Dick and P. E. Fleming, Drug Discovery Today, 2010, 15(5–6), 243 CrossRefCASPubMed.
E. M. Huber and M. Groll, Angew. Chem., Int. Ed. Engl., 2012, 51(35), 8708 CrossRefCASPubMed.
M. Bazzaro, M. K. Lee, A. Zoso, W. L. H. Stirling, A. Santillan, I.-M. Shih and R. B. S. Roden, Cancer Res., 2006, 66(7), 3754 CrossRefCASPubMed.
O. A. O'Connor, J. Wright, C. Moskowitz, J. Muzzy, B. MacGregor-Cortelli, M. Stubblefield, D. Straus, C. Portlock, P. Hamlin, E. Choi, O. Dumetrescu, D. Esseltine, E. Trehu, J. Adams, D. Schenkein and A. D. Zelenetz, J. Clin. Oncol., 2005, 23(4), 676 CrossRefPubMed.
J. Wolf, P. G. Richardson, M. Schuster, A. LeBlanc, I. B. Walters and D. S. Battleman, Clin. Adv. Hematol. Oncol., 2008, 6(10), 755–760 Search PubMed.
D. J. Kuhn, R. Z. Orlowski and C. C. Bjorklund, Curr. Cancer Drug Targets, 2011, 11(3), 285 CrossRefCASPubMed.
S. Kumar and S. V. Rajkumar, Blood, 2008, 112(6), 2177 CrossRefCASPubMed.
E. M. Huber, W. Heinemeyer and M. Groll, Structure, 2015, 23, 407–417 CrossRefCASPubMed.
X. Li, T. E. Wood, R. Sprangers, G. Jansen, N. E. Franke, X. Mao, X. Wang, Y. Zhang, S. E. Verbrugge, H. Adomat, Z. H. Li, S. Trudel, C. Chen, T. L. Religa, N. Jamal, H. Messner, J. Cloos, D. R. Rose, A. Navon, E. Guns, R. A. Batey, L. E. Kay and A. D. Schimmer, J. Natl. Cancer Inst., 2010, 102(14), 1069 CrossRefCASPubMed.
J. Li, M. Post, R. Volk, Y. Gao, M. Li, C. Metais, K. Sato, J. Tsai, W. Aird, R. D. Rosenberg, T. G. Hampton, F. Sellke, P. Carmeliet and M. Simons, Nat. Med., 2000, 6(1), 49 CrossRefCASPubMed.
A. M. Santoro, M. C. Lo Giudice, A. D'Urso, R. Lauceri, R. Purrello and D. Milardi, J. Am. Chem. Soc., 2012, 134, 10451 CrossRefCASPubMed.
F. Vallelian, J. W. Deuel, L. Opitz, C. A. Schaer, M. Puglia, M. Lönn, W. Engelsberger, S. Schauer, E. Karnaukhova, D. R. Spahn, R. Stocker, P. W. Buehler and D. J. Schaer, Cell Death Differ., 2015, 22(4), 597 CrossRefCASPubMed.
T. J. Dougherty, C. J. Gomer, B. W. Henderson, G. Jori, D. Kessel, M. Korbelik, J. Moan and Q. Peng, J. Natl. Cancer Inst., 1998, 90(12), 889 CrossRefCASPubMed.
V. Rapozzi, S. Zorzet, M. Zacchigna, E. Della Pietra, S. Cogoi and L. E. Xodo, Mol. Cancer, 2014, 13(75), 1 Search PubMed.
J. Klages, M. Coles and H. Kessler, NMR-Based Screening: A Powerful Tool in Fragment-Based Drug Discovery, in Exploiting Chemical Diversity for Drug Discovery, ed. P. A. Bartlett and M. Entzeroth, RSC Publishing, Cambridge, 2006, ch. 12, pp. 263–290 and Mol. BioSyst., 2006, vol. 2, pp. 318–332 Search PubMed.
B. Meyer and T. Peters, Angew. Chem., Int. Ed. Engl., 2003, 42(8), 864 CrossRefCASPubMed.
J. Klein, R. Meinecke, M. Mayer and B. Meyer, J. Am. Chem. Soc., 1999, 121(22), 5336 CrossRefCAS.
ACD/Percepta, version 14.0.0, Advanced Chemistry Development, Inc., Toronto, ON, Canada, 2013, http://www.acdlabs.com Search PubMed.
P. Dauber-Osguthorpe, V. A. Roberts, D. J. Osguthorpe, J. Wolff, M. Genest and A. T. Hagler, Proteins, 1998, 4, 31 CrossRefPubMed.
M. J. S. Dewar and W. Thiel, J. Am. Chem. Soc., 1977, 99, 4899 CrossRefCAS.
I. W. Davis, A. Leaver-Fay, V. B. Chen, J. N. Block, G. J. Kapral, X. Wang, L. W. Murray, W. B. Arendall, J. Snoeyink, J. S. Richardson and D. C. Richardson, Nucleic Acids Res., 2007, 35, W375 CrossRefPubMed.
M. Mayer and B. Meyer, J. Am. Chem. Soc., 2001, 123, 6108 CrossRefCASPubMed.
J. Pons, N. Evrad-Todeschi, G. Bertho, J. Gharbi Benarous, V. Tanchou, R. Benarous and J. P. Girault, Biochemistry, 2008, 47, 14 CrossRefCASPubMed.
L. Cigliano, L. de Rosa, D. Diana, R. Di Stasi, M. S. Spagnuolo, B. Maresca, R. Fattorusso and L. D. D'Andrea, RSC Adv., 2014, 4, 51353 RSC.
W. Harshbarger, C. Miller, C. Diedrich and J. Sacchettini, Structure, 2015, 23(2), 418 CrossRefCASPubMed.
J. Pei, B. H. Kim and N. V. Grishin, Nucleic Acids Res., 2008, 36, 2295 CrossRefCASPubMed.
J. Rabl, D. M. Smith, Y. Yu, S. C. Chang, A. L. Goldberg and Y. Cheng, Mol. Cell, 2008, 30(3), 360 CrossRefCASPubMed.
A. Förster, E. I. Masters, F. G. Whitby, H. Robinson and C. P. Hill, Mol. Cell, 2005, 18(5), 589 CrossRefPubMed.
A. M. Ruschak and L. E. Kay, Proc. Natl. Acad. Sci. U. S. A., 2012, 109(50), E3454 CrossRefCASPubMed.
F. G. Whitby, E. I. Masters, L. Kramer, J. R. Knowlton, Y. Yao, C. C. Wang and C. P. Hill, Nature, 2000, 408, 115 CrossRefCASPubMed.
E. Jankowska, M. Gaczynska, P. A. Osmulski, E. Sikorska, R. Rostankowski, S. Madabhushi, M. Tokmina-Lukaszewska and F. Kasprzykowski, Biopolymers, 2010, 93, 481 CrossRefCASPubMed.
J. Witkowska, P. Karpowicz, M. Gaczynska, P. A. Osmulski and E. Jankowska, J. Pept. Sci., 2014, 20, 649 CrossRefCASPubMed.
M. Groll, H. Brandstetter, H. D. Bartunik, G. Bourenkow and R. Huber, J. Mol. Biol., 2003, 327, 75 CrossRefCASPubMed.
M. Orlowski, C. Cardozo, M. C. Hidalgo and C. Michaud, Biochemistry, 1991, 30, 5999 CrossRefCASPubMed.
P. A. Osmulski, M. Hochstrasser and M. Gaczynska, Structure, 2009, 17(8), 1137 CrossRefCASPubMed.
G. G. Hammes, Y. C. Chang and T. G. Oas, Proc. Natl. Acad. Sci. U. S. A., 2009, 106(33), 13737 CrossRefCASPubMed.
R. Sprangers, X. Li, X. Mao, J. L. Rubinstein, A. D. Schimmer and L. E. Kay, Biochemistry, 2008, 47(26), 6727 CrossRefCASPubMed.
M. Gaczynska and P. A. Osmulski, Methods Enzymol., 2005, 398, 425 CAS.
A. F. Kisselev, T. N. Akopian and A. L. Goldberg, J. Biol. Chem., 1998, 273, 1982 CrossRefCASPubMed.
P. Tsvetkov, N. Reuven, C. Prives and Y. Shaul, J. Biol. Chem., 2009, 284, 26234 CrossRefCASPubMed.
M. Bajorek, D. Finley and M. H. Glickman, Curr. Biol., 2003, 13(13), 1140 CrossRefCASPubMed.
Finley, D., (2009) Annu. Rev. Biochem., 78, p. 47
Murata, S., Yashiroda, H., Tanaka, K., (2009) Nat. Rev. Mol. Cell Biol., 10, p. 104
Gallastegui, N., Groll, M., (2010) Trends Biochem. Sci., 35, p. 634
Coux, O., Tanaka, K., Goldberg, A.L., (1996) Annu. Rev. Biochem., 65, p. 801
Baumeister, W., Walz, J., Zühl, F., Seemüller, E., (1998) Cell, 92, p. 367
Glickman, M.H., Rubin, D.M., Coux, O., Wefes, I., Pfeifer, G., Cjeka, Z., Baumeister, W., Finley, D., (1998) Cell, 94 (5), p. 6156
Arendt, C.S., Hochstrasser, M., (1997) Proc. Natl. Acad. Sci. U. S. A., 94, p. 7156
Heinemeyer, W., Fischer, M., Krimmer, T., Stachon, U., Wolf, D.H., (1997) J. Biol. Chem., 272, p. 25200
Kisselev, A.F., Callard, A., Goldberg, A.L., (2006) J. Biol. Chem., 281, p. 8582
Groll, M., Ditzel, L., Löwe, J., Stock, D., Bochtler, M., Bartunik, H.D., Huber, R., (1997) Nature, 386, p. 463
Groll, M., Bajorek, M., Kohler, A., Moroder, L., Rubin, D.M., Huber, R., Glickman, M., Finley, D., (2000) Nat. Struct. Biol., 7, p. 1062
Groll, M., Huber, R., (2003) Int. J. Biochem. Cell Biol., 5, p. 606
Kohler, A., Bajorek, M., Groll, M., Moroder, L., Rubin, D.M., Huber, R., Glickman, M., Finley, D., (2001) Biochimie, 83, p. 325
McConkey, D.J., Zhu, K., (2008) Drug Resist. Updates, 11, p. 164
Lehmann, A., Jechow, K., Enenkel, C., (2008) EMBO Rep., 9 (12), p. 1237
Ben-Nissan, G., Sharon, M., (2014) Biomolecules, 4, p. 862
Dick, L.R., Fleming, P.E., (2010) Drug Discovery Today, 15 (56), p. 243
Huber, E.M., Groll, M., (2012) Angew. Chem., Int. Ed. Engl., 51 (35), p. 8708
Bazzaro, M., Lee, M.K., Zoso, A., Stirling, W.L.H., Santillan, A., Shih, I.-M., Roden, R.B.S., (2006) Cancer Res., 66 (7), p. 3754
O'Connor, O.A., Wright, J., Moskowitz, C., Muzzy, J., MacGregor-Cortelli, B., Stubblefield, M., Straus, D., Zelenetz, A.D., (2005) J. Clin. Oncol., 23 (4), p. 676
Wolf, J., Richardson, P.G., Schuster, M., LeBlanc, A., Walters, I.B., Battleman, D.S., (2008) Clin. Adv. Hematol. Oncol., 6 (10), pp. 755-760
Kuhn, D.J., Orlowski, R.Z., Bjorklund, C.C., (2011) Curr. Cancer Drug Targets, 11 (3), p. 285
Kumar, S., Rajkumar, S.V., (2008) Blood, 112 (6), p. 2177
Huber, E.M., Heinemeyer, W., Groll, M., (2015) Structure, 23, pp. 407-417
Li, X., Wood, T.E., Sprangers, R., Jansen, G., Franke, N.E., Mao, X., Wang, X., Schimmer, A.D., (2010) J. Natl. Cancer Inst., 102 (14), p. 1069
Li, J., Post, M., Volk, R., Gao, Y., Li, M., Metais, C., Sato, K., Simons, M., (2000) Nat. Med., 6 (1), p. 49
Santoro, A.M., Lo Giudice, M.C., D'Urso, A., Lauceri, R., Purrello, R., Milardi, D., (2012) J. Am. Chem. Soc., 134, p. 10451
Vallelian, F., Deuel, J.W., Opitz, L., Schaer, C.A., Puglia, M., Lönn, M., Engelsberger, W., Schaer, D.J., (2015) Cell Death Differ., 22 (4), p. 597
Dougherty, T.J., Gomer, C.J., Henderson, B.W., Jori, G., Kessel, D., Korbelik, M., Moan, J., Peng, Q., (1998) J. Natl. Cancer Inst., 90 (12), p. 889
Rapozzi, V., Zorzet, S., Zacchigna, M., Della Pietra, E., Cogoi, S., Xodo, L.E., (2014) Mol. Cancer, 13 (75), p. 1
Klages, J., Coles, M., Kessler, H., NMR-Based Screening: A Powerful Tool in Fragment-Based Drug Discovery (2006) Exploiting Chemical Diversity for Drug Discovery, pp. 263-290. , ed. A. Bartlett and M. Entzeroth, RSC Publishing, Cambridge, ch. 12, and Mol. BioSyst., 2006, 2, 318-332
Förster, A., Masters, E.I., Whitby, F.G., Robinson, H., Hill, C.P., (2005) Mol. Cell, 18 (5), p. 589
Ruschak, A.M., Kay, L.E., (2012) Proc. Natl. Acad. Sci. U. S. A., 109 (50), p. E3454
Whitby, F.G., Masters, E.I., Kramer, L., Knowlton, J.R., Yao, Y., Wang, C.C., Hill, C.P., (2000) Nature, 408, p. 115
Jankowska, E., Gaczynska, M., Osmulski, P.A., Sikorska, E., Rostankowski, R., Madabhushi, S., Tokmina-Lukaszewska, M., Kasprzykowski, F., (2010) Biopolymers, 93, p. 481
Witkowska, J., Karpowicz, P., Gaczynska, M., Osmulski, P.A., Jankowska, E., (2014) J. Pept. Sci., 20, p. 649
Groll, M., Brandstetter, H., Bartunik, H.D., Bourenkow, G., Huber, R., (2003) J. Mol. Biol., 327, p. 75
Orlowski, M., Cardozo, C., Hidalgo, M.C., Michaud, C., (1991) Biochemistry, 30, p. 5999
Osmulski, P.A., Hochstrasser, M., Gaczynska, M., (2009) Structure, 17 (8), p. 1137
Hammes, G.G., Chang, Y.C., Oas, T.G., (2009) Proc. Natl. Acad. Sci. U. S. A., 106 (33), p. 13737
Sprangers, R., Li, X., Mao, X., Rubinstein, J.L., Schimmer, A.D., Kay, L.E., (2008) Biochemistry, 47 (26), p. 6727
Kisselev, A.F., Akopian, T.N., Goldberg, A.L., (1998) J. Biol. Chem., 273, p. 1982
Tsvetkov, P., Reuven, N., Prives, C., Shaul, Y., (2009) J. Biol. Chem., 284, p. 26234
Bajorek, M., Finley, D., Glickman, M.H., (2003) Curr. Biol., 13 (13), p. 1140
<span style="font-size: 16px; font-family: 'Times New Roman', Helvetica, sans-serif; line-height: 24px;">The 20S proteasome is a barrel-shaped enzymatic assembly playing a critical role in proteome maintenance. Access of proteasome substrates to the catalytic chamber is finely regulated through gating mechanisms which involve aromatic and negatively charged residues located at the N-terminal tails of α subunits. However, despite the importance of gates in regulating proteasome function, up to now very few molecules have been shown to interfere with the equilibrium by which the catalytic channel exchanges between the open and closed states. In this light, and inspired by previous results evidencing the antiproteasome potential of cationic porphyrins, here we combine experimental (enzyme kinetics, UV stopped flow and NMR) and computational (bioinformatic analysis and docking studies) approaches to inspect proteasome inhibition by </span><span class="italic" style="font-size: 16px; font-style: italic; font-family: 'Times New Roman', Helvetica, sans-serif; line-height: 24px;">meso</span><span style="font-size: 16px; font-family: 'Times New Roman', Helvetica, sans-serif; line-height: 24px;">-tetrakis(4-</span><span class="italic" style="font-size: 16px; font-style: italic; font-family: 'Times New Roman', Helvetica, sans-serif; line-height: 24px;">N</span><span style="font-size: 16px; font-family: 'Times New Roman', Helvetica, sans-serif; line-height: 24px;">-methylpyridyl)-porphyrin (H</span><small style="font-family: 'Times New Roman', Helvetica, sans-serif; line-height: 24px;"><sub>2</sub></small><span style="font-size: 16px; font-family: 'Times New Roman', Helvetica, sans-serif; line-height: 24px;">T4) and its two </span><span class="italic" style="font-size: 16px; font-style: italic; font-family: 'Times New Roman', Helvetica, sans-serif; line-height: 24px;">ortho</span><span style="font-size: 16px; font-family: 'Times New Roman', Helvetica, sans-serif; line-height: 24px;">- and </span><span class="italic" style="font-size: 16px; font-style: italic; font-family: 'Times New Roman', Helvetica, sans-serif; line-height: 24px;">meta</span><span style="font-size: 16px; font-family: 'Times New Roman', Helvetica, sans-serif; line-height: 24px;">-isomers. We show that in a first, fast binding event H</span><small style="font-family: 'Times New Roman', Helvetica, sans-serif; line-height: 24px;"><sub>2</sub></small><span style="font-size: 16px; font-family: 'Times New Roman', Helvetica, sans-serif; line-height: 24px;">T4 accommodates in a pocket made of negatively charged and aromatic residues present in α1 (Asp10, Phe9), α3 (Tyr5), α5 (Asp9, Tyr8), α6 (Asp7, Tyr6) and α7 (Asp9, Tyr8) subunits thereby stabilizing the closed conformation. A second, slower binding mode involves interaction with the grooves which separate the α- from the β-rings. Of note, the proteasome inhibition by </span><span class="italic" style="font-size: 16px; font-style: italic; font-family: 'Times New Roman', Helvetica, sans-serif; line-height: 24px;">ortho</span><span style="font-size: 16px; font-family: 'Times New Roman', Helvetica, sans-serif; line-height: 24px;">- and </span><span class="italic" style="font-size: 16px; font-style: italic; font-family: 'Times New Roman', Helvetica, sans-serif; line-height: 24px;">meta</span><span style="font-size: 16px; font-family: 'Times New Roman', Helvetica, sans-serif; line-height: 24px;">-H</span><small style="font-family: 'Times New Roman', Helvetica, sans-serif; line-height: 24px;"><sub>2</sub></small><span style="font-size: 16px; font-family: 'Times New Roman', Helvetica, sans-serif; line-height: 24px;">T4 decreases significantly if compared to the parent compound, thus underscoring the role played by spatial distribution of the four peripheral positive charges in regulating proteasome–ligand interactions. We think that our results may pave the way to further studies aimed at rationalizing the molecular basis of novel, and more sophisticated, proteasome regulatory mechanisms.</span>
92 Records (91 escludendo Abstract e Conferenze). Impact factor totale: 391.337 (387.607 escludendo Abstract e Conferenze). Impact factor a 5 anni totale: 413.34 (410.376 escludendo Abstract e Conferenze).
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