Identification of potential small molecule binding pockets on Rho family GTPases

PLoS ONE

Volumn 7, Issue 7, 2012, Pages

  Ortiz Sanchez, Juan Manuel ^a   Nichols, Sara E ^a   Sayyah, Jacqueline ^a   Brown, Joan Heller ^a   McCammon, J Andrew ^a   Grant, Barry J ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

KINESIN; RHO GUANINE NUCLEOTIDE BINDING PROTEIN;

ARTICLE; BINDING AFFINITY; BINDING SITE; CALCULATION; CONTROLLED STUDY; CRYSTAL STRUCTURE; LIGAND BINDING; MOLECULAR DYNAMICS; NUCLEOTIDE BINDING SITE; PREDICTION; PRINCIPAL COMPONENT ANALYSIS; PROTEIN TARGETING; STRUCTURE ANALYSIS;

BINDING SITES; CELL LINE, TUMOR; CRYSTALLOGRAPHY, X-RAY; ENZYME ACTIVATION; GLIOBLASTOMA; HUMANS; MOLECULAR DYNAMICS SIMULATION; MULTIGENE FAMILY; NUCLEOTIDES; PRINCIPAL COMPONENT ANALYSIS; RHO GTP-BINDING PROTEINS; SMALL MOLECULE LIBRARIES; THROMBIN;

EUKARYOTA;

EID: 84864018934     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0040809     Document Type: Article

References (66)

1. Treisman R, Miralles F, Posern G, Zaromytidou AI, (2003) Actin dynamics control SRF activity by regulation of its coactivator MAL. Cell 113: 329-342.
2. Hall A, (2005) Rho GTPases and the control of cell behaviour. Biochem. Soc. Trans. 33: 891-895.
3. Jaffe AB, Hall A, (2005) Rho GTPases: Biochemistry and biology. Annu. Rev. Cell Dev. Biol. 21: 247-269.
4. Carlier MF, Ducruix A, Pantaloni D, (1999) Signalling to actin: the Cdc42-N-WASP-Arp2/3 connection. Chem. Biol. 6: R235-R240.
5. Hall A, Etienne-Manneville S, (2002) Rho GTPases in cell biology. Nature 420: 629-635.
6. Sprang SR, (1997) G proteins, effectors and GAPs: structure and mechanism. Curr. Opin. Struct. Biol. 7: 849-856.
7. Vetter IR, Wittinghofer A, (2001) Signal transduction- The guanine nucleotide-binding switch in three dimensions. Science 294: 1299-1304.
8. Boettner B, Van Aelst L, (2002) The role of Rho GTPases in disease development. Gene 286: 155-174.
9. Vega FM, Ridley AJ, (2008) Rho GTPases in cancer cell biology. Febs. Letters 582: 2093-2101.
10. Li HL, Deng J, Feng EG, Ma S, Zhang Y, et al. (2011) Design and Synthesis of Small Molecule RhoA Inhibitors: A New Promising Therapy for Cardiovascular Diseases? J. Med. Chem. 54: 4508-4522.
11. Kitaoka Y, Kitaoka Y, Kumai T, Lam TT, Kuribayashi K, et al. (2004) Involvement of RhoA and possible neuroprotective effect of fasudil, a Rho kinase inhibitor, in NMDA-induced neurotoxicity in the rat retina. Brain Res. 1018: 111-118.
12. Fritz G, Just I, Kaina B, (1999) Rho GTPases are over-expressed in human tumors. Int. J. Cancer 81: 682-687.
13. Ellenbroek SIJ, Collard JG, (2007) Rho GTPases: functions and association with cancer. Clin. Exp. Metastas. 24: 657-672.
14. Sahai E, Marshall CJ, (2002) Rho-Gtpases and Cancer. Nat. Rev. Cancer 2: 133-147.
15. Preudhomme C, Roumier C, Hildebrand MP, Dallery-Prudhomme E, Lantoine D, et al. (2000) Nonrandom 4p13 rearrangements of the RhoH/TTF gene, encoding a GTP-binding protein, in non-Hodgkin's lymphoma and multiple myeloma. Oncogene 19: 2023-2032.
16. Grise F, Bidaud A, Moreau V, (2009) Rho GTPases in hepatocellular carcinoma. Biochimica Et Biophysica Acta-Rev. Cancer 1795: 137-151.
17. Zhao DZ, Pothoulakis C, (2003) Rho GTPases as therapeutic targets for the treatment of inflammatory diseases. Expert Opin. Ther. Targets 7: 583-592.
18. Budzyn K, Marley PD, Sobey CG, (2006) Targeting Rho and Rho-kinase in the treatment of cardiovascular disease. Trends Pharmacol. Sci. 27: 97-104.
19. Aznar S, Fernandez-Valeron P, Espina C, Lacal JC, (2004) Rho GTPases: potential candidates for anticancer therapy. Cancer Lett. 206: 181-191.
20. Zheng Y, Nassar N, Cancelas J, Zheng J, Williams DA, (2006) Structure-function based design of small molecule inhibitors targeting Rho family GTPases. Curr. Top. Med. Chem. 6: 1109-1116.
21. Fritz G, Kaina B, (2006) Rho GTPases: Promising cellular targets for novel anticancer drugs. Curr. Cancer Drug Targets 6: 1-14.
22. Riganti C, Aldieri E, Doublier S, Bosia A, Ghigo D, (2008) Statins-mediated inhibition of Rho GTPases as a potential tool in anti-tumor therapy. Mini-Rev. Med. Chem. 8: 609-618.
23. Lu Q, Longo FM, Zhou HC, Massa SM, Chen YH, (2009) Signaling Through Rho GTPase Pathway as Viable Drug Target. Curr. Med. Chem. 16: 1355-1365.
24. Sun HW, Tong SL, He J, Wang Q, Zou L, et al. (2007) RhoA and RhoC-siRNA inhibit the proliferation and invasiveness activity of human gastric carcinoma by Rho/PI3K/Akt pathway. World Journal of Gastroenterology 13: 3517-3522.
25. Sebti SM, Der CJ, (2003) Opinion- Searching for the elusive targets of farnesyltransferase inhibitors. Nat. Rev. Cancer 3: 945-951.
26. Sebti SM, (2005) Protein farnesylation: Implications for normal physiology, malignant transformation, and cancer therapy. Cancer Cell 7: 297-300.
27. Gelb MH, Brunsveld L, Hrycyna CA, Michaelis S, Tamanoi F, et al. (2006) Therapeutic intervention based on protein prenylation and associated modifications. Nat. Chem. Biol. 2: 518-528.
28. Liao DK, Seto M, Noma K, (2007) Rho kinase (ROCK) inhibitors. J. Cardiovasc. Pharmacol. 50: 17-24.
29. Chen YT, Bannister TD, Weiser A, Griffin E, Lin L, et al. (2008) Chroman-3-amides as potent Rho kinase inhibitors. Bioorg. Med. Chem. Lett. 18: 6406-6409.
30. Schirok H, Kast R, Figueroa-Perez S, Bennabi S, Gnoth MJ, et al. (2008) Design and Synthesis of Potent and Selective Azaindole-Based Rho Kinase (ROCK) Inhibitors. ChemMedChem 3: 1893-1904.
31. Fang XG, Yin Y, Chen YT, Yao L, Wang B, et al. (2010) Tetrahydroisoquinoline Derivatives As Highly Selective and Potent Rho Kinase Inhibitors. J. Med. Chem. 53: 5727-5737.
32. Grant BJ, McCammon JA, Gorfe AA, (2010) Conformational Selection in G-Proteins Lessons from Ras and Rho. Biophys. J. 99: L87-L89.
33. Grant BJ, Gorfe AA, McCammon JA, (2010) Large conformational changes in proteins: signaling and other functions. Curr. Opin. Struct. Biol. 20: 142-147.
34. Buhrman G, Holzapfel G, Fetics S, Mattos C, (2010) Allosteric modulation of Ras positions Q61 for a direct role in catalysis. PNAS USA 107: 4931-4936.
35. Grant BJ, Lukman S, Hocker HJ, Sayyah J, Brown JH, et al. (2011) Novel Allosteric Sites on Ras for Lead Generation. PLoS One 6: e25711 1-10.
36. Perot S, Sperandio O, Miteva MA, Camproux AC, Villoutreix BO, (2010) Druggable pockets and binding site centric chemical space: a paradigm shift in drug discovery. Drug Discov. Today 15: 656-667.
37. Hamelberg D, Mongan J, McCammon JA, (2004) Accelerated molecular dynamics: A promising and efficient simulation method for biomolecules. J. Chem. Phys. 120: 11919-11929.
38. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, et al. (2000) The Protein Data Bank. Nucleic Acids Rese. 28: 235-242.
39. Grant BJ, McCammon JA, Caves LSD, Cross RA, (2007) Multivariate analysis of conserved sequence-structure relationships in kinesins: Coupling of the active site and a tubulin-binding sub-domain. J. Mol. Biol. 368: 1231-1248.
40. Brenke R, Kozakov D, Chuang GY, Beglov D, Hall D, et al. (2009) Fragment-based identification of druggable 'hot spots' of proteins using Fourier domain correlation techniques. Bioinf. 25: 621-627.
41. Halgren T, (2007) New method for fast and accurate binding-site identification and analysis. Chem. Bio. Drug Des. 69: 146-148.
42. Halgren TA, (2009) Identifying and Characterizing Binding Sites and Assessing Druggability. J. Chem. Inf. Model. 49: 377-389.
43. Snyder JT, Worthylake DK, Rossman KL, Betts L, Pruitt WM, et al. (2002) Structural basis for the selective activation of Rho GTPases by Dbl exchange factors. Nat. Struct. Biol. 9: 468-475.
44. Formaneck MS, Ma L, Cui Q, (2006) Reconciling the "old" and "new" views of protein allostery: A molecular simulation study of chemotaxis Y protein (CheY). Proteins: Struct., Funct., Bioinf. 63: 846-867.
45. Gsponer J, Christodoulou J, Cavalli A, Bui JM, Richter B, et al. (2008) A coupled equilibrium shift mechanism in calmodulin-mediated signal transduction. Structure 16: 736-746.
46. McClendon CL, Friedland G, Mobley DL, Amirkhani H, Jacobson MP, (2009) Quantifying Correlations Between Allosteric Sites in Thermodynamic Ensembles. J. Chem. Theor. Comput. 5: 2486-2502.
47. Rosnizeck IC, Graf T, Spoerner M, Trankle J, Filchtinski D, et al. (2010) Stabilizing a Weak Binding State for Effectors in the Human Ras Protein by Cyclen Complexes. Angew. Chem. Int. 49: 3830-3833 Ed.
48. Friesner RA, Banks JL, Murphy RB, Halgren TA, Klicic JJ, et al. (2004) Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J. Med. Chem. 47: 1739-1749.
49. Post GR, Collins LR, Kennedy ED, Moskowitz SA, Aragay AM, et al. (1996) Coupling of the thrombin receptor to G12 may account for selective effects of thrombin on gene expression and DNA synthesis in 1321N1 astrocytoma cells. Mol. Biol. Cell 7: 1679-1690.
50. Majumdar M, Seasholtz TM, Buckmaster C, Toksoz D, Brown JH, (1999) A Rho exchange factor mediates thrombin and Gα12-induced cytoskeletal responses. J. Biol. Chem. 274: 26815-26821.
51. Martin CB, Mahon GM, Klinger MB, Kay RJ, Symons M, et al. (2001) The thrombin receptor, PAR-1, causes transformation by activation of Rho-mediated signaling pathways. Oncogene 20: 1953-1963.
52. Grant BJ, Rodrigues APC, ElSawy KM, McCammon JA, Caves LSD, (2006) Bio3d: an R package for the comparative analysis of protein structures. Bioinf. 22: 2695-2696.
53. Caves LSD, Nguyen DT, Hubbard RE, (1991) Conformational variability of insulin: a molecular dynamics analysis. In: Goodfellow JM, editors. pp. 27-68 editor. Molecular Dynamics: Applications in molecular biology. London: The Macmillan Press Ltd.
54. vanAalten DMF, Conn DA, deGroot BL, Berendsen HJC, Findlay JBC, et al. (1997) Protein dynamics derived from clusters of crystal structures. Biophys. J. 73: 2891-2896.
55. Abseher R, Horstink L, Hilbers CW, Nilges M, (1998) Essential spaces defined by NMR structure ensembles and molecular dynamics simulation show significant overlap. Proteins: Struct., Funct., Bioinf. 31: 370-382.
56. Caves LSD, Evanseck JD, Karplus M, (1998) Locally accessible conformations of proteins: Multiple molecular dynamics simulations of crambin. Protein Sci 7: 649-666.
57. Elsawy KM, Hodgson MK, Caves LSD, (2005) The physical determinants of the DNA conformational landscape: an analysis of the potential energy surface of single-strand dinucleotides in the conformational space of duplex DNA. Nucleic Acids Res. 33: 5749-5762.
58. Grant BJ, Gorfe AA, McCammon JA, (2009) Ras Conformational Switching: Simulating Nucleotide-Dependent Conformational Transitions with Accelerated Molecular Dynamics. PLoS Comput. Biol. 5(3): e1000325.
59. Finn RD, Mistry J, Tate J, Coggill P, Heger A, et al. (2010) The Pfam protein families database. Nucleic Acids Res. 38: D211-D222.
60. Shannon CE, (1948) A Mathematical Theory of Communication. Bell System Technical Journal 27: 379-423.
61. Shenkin PS, Erman B, Mastrandrea LD, (1991) Information-Theoretical Entropy as a Measure of Sequence Variability. Proteins: Struct., Funct., Gen. 11: 297-313.
62. Hubbard S, Thornton JM, (1993) NACCESS, computer program. London: Department of Biochemistry and Molecular Biology. University College London.
63. Case DA, Cheatham TE, Darden T, Gohlke H, Luo R, et al. (2005) The Amber biomolecular simulation programs. J. Comput. Chem. 26: 1668-1688.
64. Hornak V, Abel R, Okur A, Strockbine B, Roitberg A, et al. (2006) Comparison of multiple amber force fields and development of improved protein backbone parameters. Proteins: Struct., Funct., Bioinf. 65: 712-725.
65. Hamelberg D, de Oliveira CAF, McCammon JA, (2007) Sampling of slow diffusive conformational transitions with accelerated molecular dynamics. J. Chem. Phys. 127: 155102-155111.
66. Developmental Therapeutics Program NCI/NIH website. Available:http://dtp.nci.nih.gov/branches/dscb/div2_explanation.html. Accessed 2012 January 15.