Insights into the inhibition of the p90 ribosomal S6 kinase (RSK) by the flavonol glycoside SL0101 from the 1.5 Å crystal structure of the N-terminal domain of RSK2 with bound inhibitor

Biochemistry

Volumn 51, Issue 33, 2012, Pages 6499-6510

  Utepbergenov, Darkhan ^a   Derewenda, Urszula ^a   Olekhnovich, Natalya ^a   Szukalska, Gabriela ^a,b   Banerjee, Budhaditya ^a   Hilinski, Michael K ^a   Lannigan, Deborah A ^a   Stukenberg, P Todd ^a   Derewenda, Zygmunt S ^a  

^a UNIVERSITY OF VIRGINIA   (United States)

^b UNIVERSITY OF LODZ   (Poland)

Author keywords

[No Author keywords available]

Indexed keywords

ATOMIC MODELS; BOUND INHIBITORS; CONFORMATIONAL CHANGE; FLAVONOL GLYCOSIDES; HYDROPHOBIC POCKETS; ISOFORMS; KAEMPFEROL; KINASE DOMAINS; KINASE INHIBITORS; N-TERMINAL DOMAINS; N-TERMINALS; NATURALLY OCCURRING; NUCLEOTIDE-BINDING SITES; P90 RIBOSOMAL S6 KINASE; POTENTIAL DRUG; PROTEIN MOIETY; SELECTIVE INHIBITORS; STRUCTURAL REORGANIZATION;

DISEASES; NUCLEOTIDES; SUGARS;

ENZYMES;

ENZYME INHIBITOR; FLAVONOL; GLYCOSIDE; ISOPROTEIN; KAEMPFEROL 3 O ALPHA LEVO RHAMNOPYRANOSIDE; KAEMPFEROL 3 RHAMNOSIDE; NUCLEOTIDE; PROTEIN KINASE; UNCLASSIFIED DRUG;

ARTICLE; BINDING SITE; COMPLEX FORMATION; CONFORMATION; CRYSTAL STRUCTURE; DRUG STRUCTURE; ENZYME INHIBITION; HYDROPHOBICITY; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN STRUCTURE;

BENZOPYRANS; BINDING SITES; CRYSTALLIZATION; CRYSTALLOGRAPHY, X-RAY; MANNOSIDES; MODELS, MOLECULAR; MONOSACCHARIDES; PROANTHOCYANIDINS; PROTEIN CONFORMATION; PROTEIN STRUCTURE, TERTIARY; RIBOSOMAL PROTEIN S6 KINASES, 90-KDA;

EID: 84865415698     PISSN: 00062960     EISSN: 15204995     Source Type: Journal    
DOI: 10.1021/bi300620c     Document Type: Article

References (81)

1. Manning, G., Whyte, D. B., Martinez, R., Hunter, T., and Sudarsanam, S. (2002) The protein kinase complement of the human genome Science 298, 1912-1934 (Pubitemid 35425239)
2. Fabbro, D., Cowan-Jacob, S. W., Mobitz, H., and Martiny-Baron, G. (2012) Targeting cancer with small-molecular-weight kinase inhibitors Methods Mol. Biol. 795, 1-34
3. Zhang, J., Yang, P. L., and Gray, N. S. (2009) Targeting cancer with small molecule kinase inhibitors Nat. Rev. Cancer 9, 28-39
4. Anjum, R. and Blenis, J. (2008) The RSK family of kinases: emerging roles in cellular signalling Nat. Rev. Mol. Cell Biol. 9, 747-758
5. Jones, S. W., Erikson, E., Blenis, J., Maller, J. L., and Erikson, R. L. (1988) A Xenopus ribosomal protein S6 kinase has two apparent kinase domains that are each similar to distinct protein kinases Proc. Natl. Acad. Sci. U. S. A. 85, 3377-3381
6. Pearce, L. R., Komander, D., and Alessi, D. R. (2010) The nuts and bolts of AGC protein kinases Nat. Rev. Mol. Cell Biol. 11, 9-22
7. Stratford, A. L. and Dunn, S. E. (2011) The promise and challenges of targeting RSK for the treatment of cancer Expert Opin. Ther. Targets 15, 1-4
8. Romeo, Y. and Roux, P. P. (2011) Paving the way for targeting RSK in cancer Expert Opin. Ther. Targets 15, 5-9
9. Smith, J. A., Poteet-Smith, C. E., Xu, Y., Errington, T. M., Hecht, S. M., and Lannigan, D. A. (2005) Identification of the first specific inhibitor of p90 ribosomal S6 kinase (RSK) reveals an unexpected role for RSK in cancer cell proliferation Cancer Res. 65, 1027-1034 (Pubitemid 40216465)
10. Clark, D. E., Errington, T. M., Smith, J. A., Frierson, H. F., Jr., Weber, M. J., and Lannigan, D. A. (2005) The serine/threonine protein kinase, p90 ribosomal S6 kinase, is an important regulator of prostate cancer cell proliferation Cancer Res. 65, 3108-3116 (Pubitemid 40524591)
11. Kang, S., Elf, S., Lythgoe, K., Hitosugi, T., Taunton, J., Zhou, W., Xiong, L., Wang, D., Muller, S., Fan, S., Sun, S. Y., Marcus, A. I., Gu, T. L., Polakiewicz, R. D., Chen, Z. G., Khuri, F. R., Shin, D. M., and Chen, J. (2010) p90 ribosomal S6 kinase 2 promotes invasion and metastasis of human head and neck squamous cell carcinoma cells J. Clin. Invest. 120, 1165-1177
12. Cuadrado, A. and Nebreda, A. R. (2007) New insights into RSK activation and hematopoietic cancer Cancer Cell 12, 187-189 (Pubitemid 47333422)
13. Kang, S., Dong, S., Gu, T. L., Guo, A., Cohen, M. S., Lonial, S., Khoury, H. J., Fabbro, D., Gilliland, D. G., Bergsagel, P. L., Taunton, J., Polakiewicz, R. D., and Chen, J. (2007) FGFR3 activates RSK2 to mediate hematopoietic transformation through tyrosine phosphorylation of RSK2 and activation of the MEK/ERK pathway Cancer Cell 12, 201-214 (Pubitemid 47333416)
14. Kang, S., Elf, S., Dong, S., Hitosugi, T., Lythgoe, K., Guo, A., Ruan, H., Lonial, S., Khoury, H. J., Williams, I. R., Lee, B. H., Roesel, J. L., Karsenty, G., Hanauer, A., Taunton, J., Boggon, T. J., Gu, T. L., and Chen, J. (2009) Fibroblast growth factor receptor 3 associates with and tyrosine phosphorylates p90 RSK2, leading to RSK2 activation that mediates hematopoietic transformation Mol. Cell. Biol. 29, 2105-2117
15. Mirmohammadsadegh, A., Mota, R., Gustrau, A., Hassan, M., Nambiar, S., Marini, A., Bojar, H., Tannapfel, A., and Hengge, U. R. (2007) ERK1/2 is highly phosphorylated in melanoma metastases and protects melanoma cells from cisplatin-mediated apoptosis J. Invest. Dermatol. 127, 2207-2215 (Pubitemid 47258498)
16. + exchanger-mediated cardiac ischemia-reperfusion injury Circulation 113, 2516-2523 (Pubitemid 43948030)
17. Lu, W., Liu, X., Cao, X., Xue, M., Liu, K., Zhao, Z., Shen, X., Jiang, H., Xu, Y., Huang, J., and Li, H. (2011) SHAFTS: a hybrid approach for 3D molecular similarity calculation. 2. Prospective case study in the discovery of diverse p90 ribosomal S6 protein kinase 2 inhibitors to suppress cell migration J. Med. Chem. 54, 3564-3574
18. Alessi, D. R., Sapkota, G. P., Cummings, L., Newell, F. S., Armstrong, C., Bain, J., Frodin, M., Grauert, M., Hoffmann, M., Schnapp, G., Steegmaier, M., and Cohen, P. (2007) BI-D1870 is a specific inhibitor of the p90 RSK (ribosomal S6 kinase) isoforms in vitro and in vivo Biochem. J. 401, 29-38 (Pubitemid 46114597)
19. Bain, J., Plater, L., Elliott, M., Shpiro, N., Hastie, C. J., McLauchlan, H., Klevernic, I., Arthur, J. S., Alessi, D. R., and Cohen, P. (2007) The selectivity of protein kinase inhibitors: a further update Biochem. J. 408, 297-315
20. Calderon-Montano, J. M., Burgos-Moron, E., Perez-Guerrero, C., and Lopez-Lazaro, M. (2011) A review on the dietary flavonoid kaempferol Mini Rev. Med. Chem. 11, 298-344
21. Neuhouser, M. L. (2004) Dietary flavonoids and cancer risk: evidence from human population studies Nutr. Cancer 50, 1-7 (Pubitemid 39587599)
22. Maron, D. J. (2004) Flavonoids for reduction of atherosclerotic risk Curr. Atheroscler. Rep. 6, 73-78 (Pubitemid 38898913)
23. Boly, R., Gras, T., Lamkami, T., Guissou, P., Serteyn, D., Kiss, R., and Dubois, J. (2011) Quercetin inhibits a large panel of kinases implicated in cancer cell biology Int. J. Oncol. 38, 833-842
24. Hou, D. X. and Kumamoto, T. (2010) Flavonoids as protein kinase inhibitors for cancer chemoprevention: direct binding and molecular modeling Antioxid. Redox. Signal. 13, 691-719
25. Rogers, J. C. and Williams, D. L., Jr. (1989) Kaempferol inhibits myosin light chain kinase Biochem. Biophys. Res. Commun. 164, 419-425 (Pubitemid 19269749)
26. Lee, K. M., Lee, D. E., Seo, S. K., Hwang, M. K., Heo, Y. S., Lee, K. W., and Lee, H. J. (2010) Phosphatidylinositol 3-kinase, a novel target molecule for the inhibitory effects of kaempferol on neoplastic cell transformation Carcinogenesis 31, 1338-1343
27. Kim, W., Yang, H. J., Youn, H., Yun, Y. J., Seong, K. M., and Youn, B. (2010) Myricetin inhibits Akt survival signaling and induces Bad-mediated apoptosis in a low dose ultraviolet (UV)-B-irradiated HaCaT human immortalized keratinocytes J. Radiat. Res. (Tokyo) 51, 285-296
28. Walker, E. H., Pacold, M. E., Perisic, O., Stephens, L., Hawkins, P. T., Wymann, M. P., and Williams, R. L. (2000) Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine Mol. Cell 6, 909-919
29. Suh, Y., Afaq, F., Khan, N., Johnson, J. J., Khusro, F. H., and Mukhtar, H. (2010) Fisetin induces autophagic cell death through suppression of mTOR signaling pathway in prostate cancer cells Carcinogenesis 31, 1424-1433
30. Goettert, M., Schattel, V., Koch, P., Merfort, I., and Laufer, S. (2010) Biological evaluation and structural determinants of p38alpha mitogen-activated-protein kinase and c-Jun-N-terminal kinase 3 inhibition by flavonoids ChemBioChem 11, 2579-2588
31. Ikuta, M., Kornienko, M., Byrne, N., Reid, J. C., Mizuarai, S., Kotani, H., and Munshi, S. K. (2007) Crystal structures of the N-terminal kinase domain of human RSK1 bound to three different ligands: Implications for the design of RSK1 specific inhibitors Protein Sci. 16, 2626-2635 (Pubitemid 350172748)
32. Malakhova, M., Kurinov, I., Liu, K. D., Zheng, D., DAngelo, I., Shim, J. H., Steinman, V., Bode, A. M., and Dong, Z. G. (2009) Structural diversity of the active N-terminal kinase domain of p90 ribosomal S6 kinase 2 PLoS One 4, e8044
33. Madhusudan, Akamine, P., Xuong, N. H., and Taylor, S. S. (2002) Crystal structure of a transition state mimic of the catalytic subunit of cAMP-dependent protein kinase Nat. Struct. Biol. 9, 273-277 (Pubitemid 34289899)
34. Smith, K. J., Carter, P. S., Bridges, A., Horrocks, P., Lewis, C., Pettman, G., Clarke, A., Brown, M., Hughes, J., Wilkinson, M., Bax, B., and Reith, A. (2004) The structure of MSK1 reveals a novel autoinhibitory conformation for a dual kinase protein Structure 12, 1067-1077 (Pubitemid 38748778)
35. Smith, J. A., Maloney, D. J., Hecht, S. M., and Lannigan, D. A. (2007) Structural basis for the activity of the RSK-specific inhibitor, SL0101 Bioorg. Med. Chem. 15, 5018-5034 (Pubitemid 46836823)
36. Sheffield, P., Garrard, S., and Derewenda, Z. (1999) Overcoming expression and purification problems of RhoGDI using a family of "Parallel" expression vectors Protein Expr. Purif. 15, 34-39 (Pubitemid 29321466)
37. Klock, H. E., Koesema, E. J., Knuth, M. W., and Lesley, S. A. (2008) Combining the polymerase incomplete primer extension method for cloning and mutagenesis with microscreening to accelerate structural genomics efforts Proteins 71, 982-994 (Pubitemid 351430029)
38. Maloney, D. J. and Hecht, S. M. (2005) Synthesis of a potent and selective inhibitor of p90 Rsk Org. Lett. 7, 1097-1099 (Pubitemid 40626910)
39. Otwinowski, Z. and Minor, W. (1997) Processing of X-ray diffraction data collected in oscillation mode Methods Enzymol. A276, 307-326 (Pubitemid 27085611)
40. Long, F., Vagin, A. A., Young, P., and Murshudov, G. N. (2008) BALBES: a molecular-replacement pipeline Acta Crystallogr. D64, 125-132 (Pubitemid 350308686)
41. Cohen, S. X., Ben Jelloul, M., Long, F., Vagin, A., Knipscheer, P., Lebbink, J., Sixma, T. K., Lamzin, V. S., Murshudov, G. N., and Perrakis, A. (2008) ARP/wARP and molecular replacement: the next generation Acta Crystallogr. D64, 49-60
42. Emsley, P. and Cowtan, K. (2004) Coot: model-building tools for molecular graphics Acta Crystallogr. D60, 2126-2132 (Pubitemid 41742764)
43. Adams, P. D., Afonine, P. V., Bunkoczi, G., Chen, V. B., Davis, I. W., Echols, N., Headd, J. J., Hung, L. W., Kapral, G. J., Grosse-Kunstleve, R. W., McCoy, A. J., Moriarty, N. W., Oeffner, R., Read, R. J., Richardson, D. C., Richardson, J. S., Terwilliger, T. C., and Zwart, P. H. (2010) PHENIX: a comprehensive Python-based system for macromolecular structure solution Acta Crystallogr. D66, 213-221
44. da Silva, I., Diaz, J. G., and Gonzalez-Platas, J. (2011) Structure determination of monohydrated trifolin (kaempferol 3-O-beta- d -galactopyranoside) from laboratory powder diffraction data J. Pharm. Sci. 100, 1588-1593
45. Laskowski, R. A., McArthur, M. W., Moss, D. S., and Thornton, J. M. (1993) PROCHECK: a program to check the stereochemical quality of protein structures J. Appl. Crystallogr. 26, 282-291
46. Malawski, G. A., Hillig, R. C., Monteclaro, F., Eberspaecher, U., Schmitz, A. A., Crusius, K., Huber, M., Egner, U., Donner, P., and Muller-Tiemann, B. (2006) Identifying protein construct variants with increased crystallization propensity - a case study Protein Sci. 15, 2718-2728 (Pubitemid 44833753)
47. Frodin, M., Antal, T. L., Dummler, B. A., Jensen, C. J., Deak, M., Gammeltoft, S., and Biondi, R. M. (2002) A phosphoserine/threonine-binding pocket in AGC kinases and PDK1 mediates activation by hydrophobic motif phosphorylation EMBO J. 21, 5396-5407 (Pubitemid 35231019)
48. Jensen, C. J., Buch, M. B., Krag, T. O., Hemmings, B. A., Gammeltoft, S., and Frodin, M. (1999) 90-kDa ribosomal S6 kinase is phosphorylated and activated by 3-phosphoinositide-dependent protein kinase-1 J. Biol. Chem. 274, 27168-27176
49. Vagin, A. and Teplyakov, A. (2010) Molecular replacement with MOLRE Acta Crystallogr. D66, 22-25
50. Murshudov, G. N., Skubak, P., Lebedev, A. A., Pannu, N. S., Steiner, R. A., Nicholls, R. A., Winn, M. D., Long, F., and Vagin, A. A. (2011) REFMAC5 for the refinement of macromolecular crystal structures Acta Crystallogr. D67, 355-367
51. Chan, A. W., Hutchinson, E. G., Harris, D., and Thornton, J. M. (1993) Identification, classification, and analysis of beta-bulges in proteins Protein Sci. 2, 1574-1590 (Pubitemid 23294336)
52. Liu, Y. and Gray, N. S. (2006) Rational design of inhibitors that bind to inactive kinase conformations Nat. Chem. Biol. 2, 358-364 (Pubitemid 43936934)
53. Schindler, T., Bornmann, W., Pellicena, P., Miller, W. T., Clarkson, B., and Kuriyan, J. (2000) Structural mechanism for STI-571 inhibition of abelson tyrosine kinase Science 289, 1938-1942
54. 2+ Acta Crystallogr. D66, 145-154
55. Knighton, D. R., Zheng, J. H., Ten Eyck, L. F., Ashford, V. A., Xuong, N. H., Taylor, S. S., and Sowadski, J. M. (1991) Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase Science 253, 407-414 (Pubitemid 21917165)
56. Domagala, S., Munshi, P., Ahmed, M., Guillot, B., and Jelsch, C. (2011) Structural analysis and multipole modelling of quercetin monohydrate-a quantitative and comparative study Acta Crystallogr. B67, 63-78
57. Takagi, S. and Jeffrey, G. A. (1978) Neutron-diffraction refinement of crystal-structure of alpha- l -Rhamnose Monohydrate Acta Crystallogr. B34, 2551-2555
58. Eriksson, L., Stenutz, R., and Widmalm, G. (2002) Methyl 2-O-beta- d -glucopyranosyl-alpha- l -rhamnopyranoside Acta Crystallogr. C58, O328-O329
59. Taylor, S. S. and Kornev, A. P. (2011) Protein kinases: evolution of dynamic regulatory proteins Trends Biochem. Sci. 36, 65-77
60. Huse, M. and Kuriyan, J. (2002) The conformational plasticity of protein kinases Cell 109, 275-282 (Pubitemid 34606870)
61. Karlsson, R., Zheng, J., Xuong, N., Taylor, S. S., and Sowadski, J. M. (1993) Structure of the mammalian catalytic subunit of cAMP-dependent protein kinase and an inhibitor peptide displays an open conformation Acta Crystallogr. D49, 381-388
62. Karlsson, R., Madhusudan, Taylor, S. S., and Sowadski, J. M. (1994) Intermolecular contacts in various crystal forms related to the open and closed conformational states of the catalytic subunit of cAMP-dependent protein kinase Acta Crystallogr. D50, 657-662
63. Masterson, L. R., Shi, L., Metcalfe, E., Gao, J., Taylor, S. S., and Veglia, G. (2011) Dynamically committed, uncommitted, and quenched states encoded in protein kinase A revealed by NMR spectroscopy Proc. Natl. Acad. Sci. U. S. A. 108, 6969-6974
64. Steichen, J. M., Kuchinskas, M., Keshwani, M. M., Yang, J., Adams, J. A., and Taylor, S. S. (2012) Structural basis for the regulation of protein kinase A by activation loop phosphorylation J. Biol. Chem. 287, 14672-14680
65. Hemmer, W., McGlone, M., Tsigelny, I., and Taylor, S. S. (1997) Role of the glycine triad in the ATP-binding site of cAMP-dependent protein kinase J. Biol. Chem. 272, 16946-16954 (Pubitemid 27289797)
66. Holm, L., Kaariainen, S., Wilton, C., and Plewczynski, D. (2006) Using Dali for structural comparison of proteins, Curr. Protoc. Bioinformatics Chapter 5, Unit 5.5.
67. Monod, J., Wyman, J., and Changeux, J. P. (1965) On the nature of allosteric transitions: A plausible model J. Mol. Biol. 12, 88-118
68. Changeux, J. P. (2012) Allostery and the Monod-Wyman-Changeux model After 50 years Annu. Rev. Biophys. 41, 103-133
69. Changeux, J. P. and Edelstein, S. (2011) Conformational selection or induced fit? 50 years of debate resolved F1000 Biol. Rep. 3, 19
70. Koshland, D. E., Jr., Nemethy, G., and Filmer, D. (1966) Comparison of experimental binding data and theoretical models in proteins containing subunits Biochemistry 5, 365-385
71. Copeland, R. A. (2011) Conformational adaptation in drug-target interactions and residence time Future Med. Chem. 3, 1491-1501
72. Sicheri, F., Moarefi, I., and Kuriyan, J. (1997) Crystal structure of the Src family tyrosine kinase Hck Nature 385, 602-609 (Pubitemid 27087567)
73. Zhao, B., Smallwood, A., Yang, J., Koretke, K., Nurse, K., Calamari, A., Kirkpatrick, R. B., and Lai, Z. (2008) Modulation of kinase-inhibitor interactions by auxiliary protein binding: crystallography studies on Aurora A interactions with VX-680 and with TPX2 Protein Sci. 17, 1791-1797
74. Natarajan, S. R., Heller, S. T., Nam, K., Singh, S. B., Scapin, G., Patel, S., Thompson, J. E., Fitzgerald, C. E., and OKeefe, S. J. (2006) p38 MAP kinase inhibitors. Part 6: 2-arylpyridazin-3-ones as templates for inhibitor design Bioorg. Med. Chem. Lett. 16, 5809-5813 (Pubitemid 44486736)
75. Eisinger-Mathason, T. S., Andrade, J., Groehler, A. L., Clark, D. E., Muratore-Schroeder, T. L., Pasic, L., Smith, J. A., Shabanowitz, J., Hunt, D. F., Macara, I. G., and Lannigan, D. A. (2008) Codependent functions of RSK2 and the apoptosis-promoting factor TIA-1 in stress granule assembly and cell survival Mol. Cell 31, 722-736
76. Pasic, L., Eisinger-Mathason, T. S., Velayudhan, B. T., Moskaluk, C. A., Brenin, D. R., Macara, I. G., and Lannigan, D. A. (2011) Sustained activation of the HER1-ERK1/2-RSK signaling pathway controls myoepithelial cell fate in human mammary tissue Genes Dev. 25, 1641-1653
77. Stratford, A. L., Fry, C. J., Desilets, C., Davies, A. H., Cho, Y. Y., Li, Y., Dong, Z., Berquin, I. M., Roux, P. P., and Dunn, S. E. (2008) Y-box binding protein-1 serine 102 is a downstream target of p90 ribosomal S6 kinase in basal-like breast cancer cells Breast Cancer Res. 10, R99
78. Godeny, M. D. and Sayeski, P. P. (2006) ERK1/2 regulates ANG II-dependent cell proliferation via cytoplasmic activation of RSK2 and nuclear activation of elk1 Am. J. Physiol. Cell Physiol. 291, C1308-1317
79. Chen, S. and Mackintosh, C. (2009) Differential regulation of NHE1 phosphorylation and glucose uptake by inhibitors of the ERK pathway and p90RSK in 3T3-L1 adipocytes Cell Signal. 21, 1984-1993
80. + exchanger regulation for cardiac protection: a RSKy approach? Curr. Opin. Pharmacol. 8, 133-140
81. Nguyen, T. L., Gussio, R., Smith, J. A., Lannigan, D. A., Hecht, S. M., Scudiero, D. A., Shoemaker, R. H., and Zaharevitz, D. W. (2006) Homology model of RSK2 N-terminal kinase domain, structure-based identification of novel RSK2 inhibitors, and preliminary common pharmacophore Bioorg. Med. Chem. 14, 6097-6105 (Pubitemid 44080569)