Changes in signal transducer and activator of transcription 3 (STAT3) dynamics induced by complexation with pharmacological inhibitors of Src homology 2 (SH2) domain dimerization

Journal of Biological Chemistry

Volumn 289, Issue 47, 2014, Pages 32538-32547

  Resetca, Diana ^a   Haftchenary, Sina ^b   Gunning, Patrick T ^b   Wilson, Derek J ^a  

^a YORK UNIVERSITY   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

DEUTERIUM; DIMERIZATION; DRUG THERAPY; ELECTROSPRAY IONIZATION; MASS SPECTROMETRY; SALICYLIC ACID; TRANSDUCERS;

EXPERIMENTAL CONFIRMATION; HYDROGEN-DEUTERIUM EXCHANGE; NUCLEAR LOCALIZATION; PHARMACOLOGICAL INHIBITORS; PHYSIOLOGICAL CONDITION; PROTEIN-LIGAND INTERACTIONS; SMALL MOLECULE INHIBITOR; SRC HOMOLOGY 2 DOMAINS;

TRANSCRIPTION;

BP 1 102; DEUTERIUM; PROTEIN SH2; SALICYLIC ACID; SF 1 066; STAT3 PROTEIN; UNCLASSIFIED DRUG; AMINOSALICYLIC ACID DERIVATIVE; BP-1-102; MOLECULAR LIBRARY; PROTEIN BINDING; SF-1-066; SULFONAMIDE;

ALLOSTERISM; ARTICLE; BINDING SITE; COMPLEX FORMATION; COMPUTER MODEL; CONTROLLED STUDY; CRYSTAL STRUCTURE; DEUTERIUM HYDROGEN EXCHANGE; DEUTERIUM HYDROGEN EXCHANGE MASS SPECTROMETRY; DIMERIZATION; ELECTROSPRAY MASS SPECTROMETRY; EVOLUTION; HUMAN; MASS SPECTROMETRY; MICROFLUIDICS; MOLECULAR DOCKING; MOUSE; NONHUMAN; PROTEIN DOMAIN; PROTEIN INTERACTION; PROTEIN LIGAND INTERACTION; TIME RESOLVED ELECTROSPRAY MASS SPECTROMETRY; AMINO ACID SEQUENCE; ANIMAL; CHEMICAL STRUCTURE; CHEMISTRY; DRUG EFFECTS; GENETICS; METABOLISM; MOLECULAR DYNAMICS; MOLECULAR GENETICS; MOLECULAR LIBRARY; PHARMACOLOGY; PROTEIN MULTIMERIZATION; SRC HOMOLOGY DOMAIN;

AMINO ACID SEQUENCE; AMINOSALICYLIC ACIDS; ANIMALS; BINDING SITES; DEUTERIUM EXCHANGE MEASUREMENT; MICE; MODELS, MOLECULAR; MOLECULAR DYNAMICS SIMULATION; MOLECULAR SEQUENCE DATA; MOLECULAR STRUCTURE; PROTEIN BINDING; PROTEIN MULTIMERIZATION; SMALL MOLECULE LIBRARIES; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION; SRC HOMOLOGY DOMAINS; STAT3 TRANSCRIPTION FACTOR; SULFONAMIDES;

EID: 84911370403     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M114.595454     Document Type: Article

References (34)

1. Yu, H., Pardoll, D., and Jove, R. (2009) STATs in cancer inflammation and immunity: a leading role for STAT3. Nat. Rev. Cancer 9, 798-809
2. Bromberg, J., and Darnell, J. E., Jr. (2000) The role of STATs in transcriptional control and their impact on cellular function. Oncogene 19, 2468-2473
3. Haan, S., Hemmann, U., Hassiepen, U., Schaper, F., Schneider-Mergener, J., Wollmer, A., Heinrich, P. C., and Grötzinger, J. (1999) Characterization and binding specificity of the monomeric STAT3-SH2 domain. J. Biol. Chem. 274, 1342-1348
4. Ladbury, J. E., Lemmon, M. A., Zhou, M., Green, J., Botfield, M. C., and Schlessinger, J. (1995) Measurement of the binding of tyrosyl phosphopeptides to SH2 domains: a reappraisal. Proc. Natl. Acad. Sci. U.S.A. 92, 3199-3203
5. Page, B. D., Ball, D. P., and Gunning, P. T. (2011) Signal transducer and activator of transcription 3 inhibitors: a patent review. Expert Opin. Ther. Pat. 21, 65-83
6. Moran, M. F., Koch, C. A., Anderson, D., Ellis, C., England, L., Martin, G. S., and Pawson, T. (1990) Src homology region 2 domains direct protein-protein interactions in signal transduction. Proc. Natl. Acad. Sci. U.S.A. 87, 8622-8626
7. Finerty, P. J., Jr., Mittermaier, A. K., Muhandiram, R., Kay, L. E., and Forman-Kay, J. D. (2005) NMR dynamics-derived insights into the binding properties of a peptide interacting with an SH2 domain. Biochemistry 44, 694-703
8. Zhang, X., Yue, P., Page, B. D., Li, T., Zhao, W., Namanja, A. T., Paladino, D., Zhao, J., Chen, Y., Gunning, P. T., and Turkson, J. (2012) Orally bioavailable small-molecule inhibitor of transcription factor Stat3 regresses human breast and lung cancer xenografts. Proc. Natl. Acad. Sci. U.S.A. 109, 9623-9628
9. Fletcher, S., Page, B. D., Zhang, X., Yue, P., Li, Z. H., Sharmeen, S., Singh, J., Zhao, W., Schimmer, A. D., Trudel, S., Turkson, J., and Gunning, P. T. (2011) Antagonism of the Stat3-Stat3 protein dimer with salicylic acid based small molecules. ChemMedChem 6, 1459-1470
10. Page, B. D., Fletcher, S., Yue, P., Li, Z., Zhang, X., Sharmeen, S., Datti, A., Wrana, J. L., Trudel, S., Schimmer, A. D., Turkson, J., and Gunning, P. T. (2011) Identification of a non-phosphorylated, cell permeable, small molecule ligand for the Stat3 SH2 domain. Bioorg. Med. Chem. Lett. 21, 5605-5609
11. Zhang, X., Yue, P., Fletcher, S., Zhao, W., Gunning, P. T., and Turkson, J. (2010) A novel small-molecule disrupts Stat3 SH2 domain-phosphotyrosine interactions and Stat3-dependent tumor processes. Biochem. Pharmacol. 79, 1398-1409
12. Nkansah, E., Shah, R., Collie, G. W., Parkinson, G. N., Palmer, J., Rahman, K. M., Bui, T. T., Drake, A. F., Husby, J., Neidle, S., Zinzalla, G., Thurston, D. E., and Wilderspin, A. F. (2013) Observation of unphosphorylated STAT3 core protein binding to target dsDNA by PEMSA and x-ray crystallography. FEBS Lett. 587, 833-839
13. Ren, Z., Mao, X., Mertens, C., Krishnaraj, R., Qin, J., Mandal, P. K., Romanowski, M. J., McMurray, J. S., and Chen, X. (2008) Crystal structure of unphosphorylated STAT3 core fragment. Biochem. Biophys. Res. Commun. 374, 1-5
14. Becker, S., Groner, B., and Müller, C. W. (1998) Three-dimensional structure of the Stat3β homodimer bound to DNA. Nature 394, 145-151
15. Resetca, D., and Wilson, D. J. (2013) Characterizing rapid, activity-linked conformational transitions in proteins via sub-second hydrogen deuterium exchange mass spectrometry. FEBS J. 280, 5616-5625
16. Liuni, P., Jeganathan, A., and Wilson, D. J. (2012) Conformer selection and intensified dynamics during catalytic turnover in chymotrypsin. Angew. Chem. Int. Ed. Engl. 51, 9666-9669
17. Rob, T., Gill, P. K., Golemi-Kotra, D., and Wilson, D. J. (2013) An electrospray ms-coupled microfluidic device for sub-second hydrogen/deuterium exchange pulse-labelling reveals allosteric effects in enzyme inhibition. Lab. Chip 13, 2528-2532
18. Rob, T., Liuni, P., Gill, P. K., Zhu, S., Balachandran, N., Berti, P. J., and Wilson, D. J. (2012) Measuring dynamics in weakly structured regions of proteins using microfluidics-enabled subsecond H/D exchange mass spectrometry. Anal. Chem. 84, 3771-3779
19. Wilson, D. J., and Konermann, L. (2003) A capillary mixer with adjustable reaction chamber volume for millisecond time-resolved studies by electrospray mass spectrometry. Anal. Chem. 75, 6408-6414
20. Strohalm, M., Kavan, D., Novák, P., Volný, M., and Havlícek, V. (2010) mMass 3: a cross-platform software environment for precise analysis of mass spectrometric data. Anal. Chem. 82, 4648-4651
21. Montelione, G. T., Zheng, D., Huang, Y. J., Gunsalus, K. C., and Szyperski, T. (2000) Protein NMR spectroscopy in structural genomics. Nat. Struct. Biol. 7, (suppl.) 982-985
22. Fletcher, S., Singh, J., Zhang, X., Yue, P., Page, B. D., Sharmeen, S., Shahani, V. M., Zhao, W., Schimmer, A. D., Turkson, J., and Gunning, P. T. (2009) Disruption of transcriptionally active Stat3 dimers with non-phosphorylated, salicylic acid-based small molecules: potent in vitro and tumor cell activities. Chembiochem 10, 1959-1964
23. Engen, J. R., Gmeiner, W. H., Smithgall, T. E., and Smith, D. L. (1999) Hydrogen exchange shows peptide binding stabilizes motions in Hck SH2. Biochemistry 38, 8926-8935
24. Shoelson, S. E., Sivaraja, M., Williams, K. P., Hu, P., Schlessinger, J., and Weiss, M. A. (1993) Specific phosphopeptide binding regulates a conformational change in the PI 3-kinase SH2 domain associated with enzyme activation. EMBO J. 12, 795-802
25. Ma, J., Zhang, T., Novotny-Diermayr, V., Tan, A. L., and Cao, X. (2003) A novel sequence in the coiled-coil domain of Stat3 essential for its nuclear translocation. J. Biol. Chem. 278, 29252-29260
26. Horvath, C. M., Wen, Z., and Darnell, J. E., Jr. (1995) A STAT protein domain that determines DNA sequence recognition suggests a novel DNA-binding domain. Genes Dev. 9, 984-994
27. Ma, B., Tsai, C. J., Haliloʇlu, T., and Nussinov, R. (2011) Dynamic allostery: linkers are not merely flexible. Structure 19, 907-917
28. Wong, L., Lieser, S. A., Miyashita, O., Miller, M., Tasken, K., Onuchic, J. N., Adams, J. A., Woods, V. L., Jr., and Jennings, P. A. (2005) Coupled motions in the SH2 and kinase domains of Csk control Src phosphorylation. J. Mol. Biol. 351, 131-143
29. Hamuro, Y., Wong, L., Shaffer, J., Kim, J. S., Stranz, D. D., Jennings, P. A., Woods, V. L., Jr., and Adams, J. A. (2002) Phosphorylation driven motions in the COOH-terminal Src kinase, CSK, revealed through enhanced hydrogen-deuterium exchange and mass spectrometry (DXMS). J. Mol. Biol. 323, 871-881
30. Zhang, J., Adrián, F. J., Jahnke, W., Cowan-Jacob, S. W., Li, A. G., Iacob, R. E., Sim, T., Powers, J., Dierks, C., Sun, F., Guo, G. R., Ding, Q., Okram, B., Choi, Y., Wojciechowski, A., Deng, X., Liu, G., Fendrich, G., Strauss, A., Vajpai, N., Grzesiek, S., Tuntland, T., Liu, Y., Bursulaya, B., Azam, M., Manley, P. W., Engen, J. R., Daley, G. Q., Warmuth, M., and Gray, N. S. (2010) Targeting Bcr-Abl by combining allosteric with ATP-binding-site inhibitors. Nature 463, 501-506
31. Iacob, R. E., Pene-Dumitrescu, T., Zhang, J., Gray, N. S., Smithgall, T. E., and Engen, J. R. (2009) Conformational disturbance in Abl kinase upon mutation and deregulation. Proc. Natl. Acad. Sci. U.S.A. 106, 1386-1391
32. Panjarian, S., Iacob, R. E., Chen, S., Wales, T. E., Engen, J. R., and Smithgall, T. E. (2013) Enhanced SH3/linker interaction overcomes Abl kinase activation by gatekeeper and myristic acid binding pocket mutations and increases sensitivity to small molecule inhibitors. J. Biol. Chem. 288, 6116-6129
33. Inghirami, G., Chiarle, R., Simmons, W. J., Piva, R., Schlessinger, K., and Levy, D. E. (2005) New and old functions of STAT3: a pivotal target for individualized treatment of cancer. Cell Cycle 4, 1131-1133
34. Kabsch, W., and Sander, C. (1983) Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 22, 2577-2637