Identification of an allosteric pocket on human Hsp70 reveals a mode of inhibition of this therapeutically important protein

Chemistry and Biology

Volumn 20, Issue 12, 2013, Pages 1469-1480

  Rodina, Anna ^a   Patel, Pallav D ^a,b   Kang, Yanlong ^a   Patel, Yogita ^c   Baaklini, Imad ^c   Wong, Michael J H ^c   Taldone, Tony ^a   Yan, Pengrong ^a   Yang, Chenghua ^a   Maharaj, Ronnie ^a   Gozman, Alexander ^a   Patel, Maulik R ^a   Patel, Hardik J ^a   Chirico, William ^d   Erdjument Bromage, Hediye ^a   Talele, Tanaji T ^b   Young, Jason C ^c   Chiosis, Gabriela ^a  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^b ST JOHN'S UNIVERSITY   (United States)

^c MCGILL UNIVERSITY   (Canada)

^d SUNY Downstate Medical Center   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HEAT SHOCK PROTEIN 70; HEAT SHOCK PROTEIN 90;

ALLOSTERISM; AMINO ACID SEQUENCE; ARTICLE; BINDING AFFINITY; BIOLOGICAL ACTIVITY; BIOLOGICAL FUNCTIONS; CANCER CELL; COMPLEX FORMATION; CONFORMATIONAL TRANSITION; CRYSTAL STRUCTURE; CYTOSOL; HYDROPHILICITY; HYDROPHOBICITY; LIGAND BINDING; NONHUMAN; NUCLEOTIDE BINDING SITE; PHENOTYPE; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE;

ALLOSTERIC SITE; CELL LINE, TUMOR; DNA-BINDING PROTEINS; DRUG DISCOVERY; HSP70 HEAT-SHOCK PROTEINS; HSP90 HEAT-SHOCK PROTEINS; HUMANS; MODELS, MOLECULAR; PROTEIN STRUCTURE, TERTIARY; STRUCTURAL HOMOLOGY, PROTEIN; TRANSCRIPTION FACTORS;

EID: 84890860170     PISSN: 10745521     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.chembiol.2013.10.008     Document Type: Article

References (39)

1. I. Baaklini, M.J. Wong, C. Hantouche, Y. Patel, A. Shrier, and J.C. Young The DNAJA2 substrate release mechanism is essential for chaperone-mediated folding J. Biol. Chem. 287 2012 41939 41954
2. R. Bagatell, G.D. Paine-Murrieta, C.W. Taylor, E.J. Pulcini, S. Akinaga, I.J. Benjamin, and L. Whitesell Induction of a heat shock factor 1-dependent stress response alters the cytotoxic activity of hsp90-binding agents Clin. Cancer Res. 6 2000 3312 3318
3. M.K. Bhangoo, S. Tzankov, A.C. Fan, K. Dejgaard, D.Y. Thomas, and J.C. Young Multiple 40-kDa heat-shock protein chaperones function in Tom70-dependent mitochondrial import Mol. Biol. Cell 18 2007 3414 3428
4. E.B. Bertelsen, L. Chang, J.E. Gestwicki, and E.R. Zuiderweg Solution conformation of wild-type E. coli Hsp70 (DnaK) chaperone complexed with ADP and substrate Proc. Natl. Acad. Sci. USA 106 2009 8471 8476
5. A. Bhattacharya, A.V. Kurochkin, G.N. Yip, Y. Zhang, E.B. Bertelsen, and E.R. Zuiderweg Allostery in Hsp70 chaperones is transduced by subdomain rotations J. Mol. Biol. 388 2009 475 490
6. J.L. Brodsky, and G. Chiosis Hsp70 molecular chaperones: emerging roles in human disease and identification of small molecule modulators Curr. Top. Med. Chem. 6 2006 1215 1225
7. L. Chang, Y. Miyata, P.M. Ung, E.B. Bertelsen, T.J. McQuade, H.A. Carlson, E.R. Zuiderweg, and J.E. Gestwicki Chemical screens against a reconstituted multiprotein complex: myricetin blocks DnaJ regulation of DnaK through an allosteric mechanism Chem. Biol. 18 2011 210 221
8. G. Chiosis, M.N. Timaul, B. Lucas, P.N. Munster, F.F. Zheng, L. Sepp-Lorenzino, and N. Rosen A small molecule designed to bind to the adenine nucleotide pocket of Hsp90 causes Her2 degradation and the growth arrest and differentiation of breast cancer cells Chem. Biol. 8 2001 289 299
9. M. Daugaard, M. Rohde, and M. Jäättelä The heat shock protein 70 family: Highly homologous proteins with overlapping and distinct functions FEBS Lett. 581 2007 3702 3710
10. K.M. Flaherty, S.M. Wilbanks, C. DeLuca-Flaherty, and D.B. McKay Structural basis of the 70-kilodalton heat shock cognate protein ATP hydrolytic activity. II. Structure of the active site with ADP or ATP bound to wild type and mutant ATPase fragment J. Biol. Chem. 269 1994 12899 12907
11. T.A. Halgren Identifying and characterizing binding sites and assessing druggability J. Chem. Inf. Model. 49 2009 377 389
12. C.M. Haney, C. Schneider, B. Beck, J.L. Brodsky, and A. Dömling Identification of Hsp70 modulators through modeling of the substrate binding domain Bioorg. Med. Chem. Lett. 19 2009 3828 3831
13. H. He, D. Zatorska, J. Kim, J. Aguirre, L. Llauger, Y. She, N. Wu, R.M. Immormino, D.T. Gewirth, and G. Chiosis Identification of potent water soluble purine-scaffold inhibitors of the heat shock protein 90 J. Med. Chem. 49 2006 381 390
14. Kang, Y., Taldone, T., Rodina, A., Patel, P.D. and Chiosis, G. June 2012. Heat shock protein binding compounds, compositions, and methods for making and using same. U.S. patent EP2467142 A2.
15. R. Kityk, J. Kopp, I. Sinning, and M.P. Mayer Structure and dynamics of the ATP-bound open conformation of Hsp70 chaperones Mol. Cell 48 2012 863 874
16. J. Li, R. Abel, K. Zhu, Y. Cao, S. Zhao, and R.A. Friesner The VSGB 2.0 model: a next generation energy model for high resolution protein structure modeling Proteins 79 2011 2794 2812
17. Q. Liu, E.J. Levy, and W.J. Chirico N-Ethylmaleimide inactivates a nucleotide-free Hsp70 molecular chaperone J. Biol. Chem. 271 1996 29937 29944
18. M.P. Mayer, and B. Bukau Hsp70 chaperones: cellular functions and molecular mechanism Cell. Mol. Life Sci. 62 2005 670 684
19. Y. Miyata, J.N. Rauch, U.K. Jinwal, A.D. Thompson, S. Srinivasan, C.A. Dickey, and J.E. Gestwicki Cysteine reactivity distinguishes redox sensing by the heat-inducible and constitutive forms of heat shock protein 70 Chem. Biol. 19 2012 1391 1399
20. K. Moulick, C.C. Clement, J. Aguirre, J. Kim, Y. Kang, S. Felts, and G. Chiosis Synthesis of a red-shifted fluorescence polarization probe for Hsp90 Bioorg. Med. Chem. Lett. 16 2006 4515 4518
21. K. Moulick, J.H. Ahn, H. Zong, A. Rodina, L. Cerchietti, E.M. Gomes DaGama, E. Caldas-Lopes, K. Beebe, F. Perna, and K. Hatzi et al. Affinity-based proteomics reveal cancer-specific networks coordinated by Hsp90 Nat. Chem. Biol. 7 2011 818 826
22. S. Patury, Y. Miyata, and J.E. Gestwicki Pharmacological targeting of the Hsp70 chaperone Curr. Top. Med. Chem. 9 2009 1337 1351
23. M.V. Powers, K. Jones, C. Barillari, I. Westwood, R.L. van Montfort, and P. Workman Targeting HSP70: the second potentially druggable heat shock protein and molecular chaperone? Cell Cycle 9 2010 1542 1550
24. A.-L. Rérole, G. Jego, and C. Garrido Hsp70: anti-apoptotic and tumorigenic protein Methods Mol. Biol. 787 2011 205 230
25. C. Rösli, J.N. Rybak, D. Neri, and G. Elia Quantitative recovery of biotinylated proteins from streptavidin-based affinity chromatography resins Methods Mol. Biol. 418 2008 89 100
26. J. Singh, R.C. Petter, T.A. Baillie, and A. Whitty The resurgence of covalent drugs Nat. Rev. Drug Discov. 10 2011 307 317
27. M. Sriram, J. Osipiuk, B. Freeman, R. Morimoto, and A. Joachimiak Human Hsp70 molecular chaperone binds two calcium ions within the ATPase domain Structure 5 1997 403 414
28. S. Tzankov, M.J.H. Wong, K. Shi, C. Nassif, and J.C. Young Functional divergence between co-chaperones of Hsc70 J. Biol. Chem. 283 2008 27100 27109
29. M. Vilenchik, D. Solit, A. Basso, H. Huezo, B. Lucas, H. He, N. Rosen, C. Spampinato, P. Modrich, and G. Chiosis Targeting wide-range oncogenic transformation via PU24FCl, a specific inhibitor of tumor Hsp90 Chem. Biol. 11 2004 787 797
30. H. Wegele, L. Müller, and J. Buchner Hsp70 and Hsp90 - a relay team for protein folding Rev. Physiol. Biochem. Pharmacol. 151 2004 1 44
31. D.S. Williamson, J. Borgognoni, A. Clay, Z. Daniels, P. Dokurno, M.J. Drysdale, N. Foloppe, G.L. Francis, C.J. Graham, and R. Howes et al. Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design J. Med. Chem. 52 2009 1510 1513
32. M. Wisniewska, T. Karlberg, L. Lehtiö, I. Johansson, T. Kotenyova, M. Moche, and H. Schüler Crystal structures of the ATPase domains of four human Hsp70 isoforms: HSPA1L/Hsp70-hom, HSPA2/Hsp70-2, HSPA6/Hsp70B', and HSPA5/BiP/GRP78 PLoS ONE 5 2010 e8625
33. B. Wallner, and A. Elofsson All are not equal: a benchmark of different homology modeling programs Protein Sci. 14 2005 1315 1327
34. H.J. Woo, J. Jiang, E.M. Lafer, and R. Sousa ATP-induced conformational changes in Hsp70: molecular dynamics and experimental validation of an in silico predicted conformation Biochemistry 48 2009 11470 11477
35. P. Workman, F. Burrows, L. Neckers, and N. Rosen Drugging the cancer chaperone HSP90: combinatorial therapeutic exploitation of oncogene addiction and tumor stress Ann. N Y Acad. Sci. 1113 2007 202 216
36. L.J. Worrall, and M.D. Walkinshaw Crystal structure of the C-terminal three-helix bundle subdomain of C. elegans Hsp70 Biochem. Biophys. Res. Commun. 357 2007 105 110
37. J.C. Young, V.R. Agashe, K. Siegers, and F.U. Hartl Pathways of chaperone-mediated protein folding in the cytosol Nat. Rev. Mol. Cell Biol. 5 2004 781 791
38. X. Zhu, X. Zhao, W.F. Burkholder, A. Gragerov, C.M. Ogata, M.E. Gottesman, and W.A. Hendrickson Structural analysis of substrate binding by the molecular chaperone DnaK Science 272 1996 1606 1614
39. J. Zou, Y. Guo, T. Guettouche, D.F. Smith, and R. Voellmy Repression of heat shock transcription factor HSF1 activation by HSP90 (HSP90 complex) that forms a stress-sensitive complex with HSF1 Cell 94 1998 471 480