Abundance of intrinsic disorder in protein associated with cardiovascular disease

Biochemistry

Volumn 45, Issue 35, 2006, Pages 10448-10460

  Cheng, Yugong ^a   LeGall, Tanguy ^a   Oldfield, Christopher J ^b   Dunker, A Keith ^a,b   Uversky, Vladimir N ^a,b,c  

^a Molecular Kinetics Inc   (United States)

^b INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c INSTITUTE FOR BIOLOGICAL INSTRUMENTATION   (Russian Federation)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACIDS; BIOCOMMUNICATIONS; CARDIOVASCULAR SYSTEM; CONFORMATIONS; MEDICAL PROBLEMS; NEURAL NETWORKS; TUMORS;

CARDIOVASCULAR DISEASES (CVD); CHARGE-HYDROPATHY PLOT (CH PLOT) ANALYSIS; CUMULATIVE DISTRIBUTION FUNCTION (CDF); PROTEIN-PROTEIN INTERACTIONS;

PROTEINS;

ARGININE; GLUTAMIC ACID; GLUTAMINE; ISOLEUCINE; PHENYLALANINE; PROLINE; SERINE; TRYPTOPHAN; TYROSINE; VALINE;

ALPHA HELIX; ARTICLE; CANCER; CARDIOVASCULAR DISEASE; MOLECULAR RECOGNITION; NERVE CELL NETWORK; PRIORITY JOURNAL; PROTEIN DEFECT; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN SECONDARY STRUCTURE; PROTEIN TERTIARY STRUCTURE; REGULATORY MECHANISM; SIGNAL TRANSDUCTION; SWISS-PROT;

3',5'-CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE; CARDIOVASCULAR DISEASES; COMPUTER SIMULATION; DATABASES, PROTEIN; FIBRINOGEN; HIRUDINS; HUMANS; MODELS, MOLECULAR; PROTEIN CONFORMATION; PROTEIN STRUCTURE, TERTIARY; PROTEINS; SEQUENCE ANALYSIS, PROTEIN; STRUCTURE-ACTIVITY RELATIONSHIP; THROMBIN;

EUKARYOTA;

EID: 33748280715     PISSN: 00062960     EISSN: None     Source Type: Journal    
DOI: 10.1021/bi060981d     Document Type: Article

References (101)

1. American Heart Association (2005) Dallas.
2. Romero, P., Obradovic, Z., Kissinger, C. R., Villafranca, J. E., Garner, E., Guilliot, S., and Dunker, A. K. (1998) Thousands of proteins likely to have long disordered regions, Pac. Symp. Biocomput. '98, 437-48.
3. Wright, P. E., and Dyson, H. J. (1999) Intrinsically unstructured proteins: Re-assessing the protein structure-function paradigm, J. Mol. Biol. 293, 321-31.
4. Uversky, V. N., Gillespie, J. R., and Fink, A. L. (2000) Why are "natively unfolded" proteins unstructured under physiologic conditions? Proteins 41, 415-27.
5. Dunker, A. K., Lawson, J. D., Brown, C. J., Williams, R. M., Romero, P., Oh, J. S., Oldfield, C. J., Campen, A. M., Ratliff, C. M., Hipps, K. W., Ausio, J., Nissen, M. S., Reeves, R., Kang, C, Kissinger, C. R., Bailey, R. W., Griswold, M. D., Chiu, W., Garner, E. C., and Obradovic, Z. (2001) Intrinsically disordered protein, J. Mol. Graphics Modell. 19, 26-59.
6. Dunker, A. K., Brown, C. J., Lawson, J. D., Iakoucheva, L. M., and Obradovic, Z. (2002) Intrinsic disorder and protein function, Biochemistry 41, 6573-82.
7. Tompa, P. (2002) Intrinsically unstructured proteins, Trends Biochem. Sci. 27, 527-33.
8. Uversky, V. N. (2002) Natively unfolded proteins: A point where biology waits for physics, Protein Sci. 11, 739-56.
9. Uversky, V. N. (2002) What does it mean to be natively unfolded? Eur. J. Biochem. 269, 2-12.
10. Uversky, V. N. (2003) Protein folding revisited. A polypeptide chain at the folding-misfolding-nonfolding cross-roads: Which way to go? Cell. Mol. Life Sci. 60, 1852-71.
11. Daughdrill, G. W., Pielak, G. J., Uversky, V. N., Cortese, M. S., and Dunker, A. K. (2005) Natively disordered proteins, in Handbook of Protein Folding (Buchner, J., and Kiefhaber, T., Eds.) pp 271-353, Wiley-VCH, Verlag GmbH & Co. KGaA, Weinheim, Germany.
12. Dunker, A. K., and Obradovic, Z. (2001) The protein trinity: Linking function and disorder, Nat. Biotechnol. 19, 805-6.
13. Romero, P., Obradovic, Z., and Dunker, A. K. (1997) Sequence data analysis for long disordered regions prediction in the calcineurin family, Genome Inf. 8, 110-24.
14. Romero, P., Obradovic, Z., Kissinger, C., Villafranca, J. E., and Dunker, A. K. (1997) Identifying disordered regions in proteins from amino acid sequence, 1997 Proceedings of the International Conference on Neural Networks 1, 90-5.
15. Dunker, A. K., Garner, E., Guilliot, S., Romero, P., Albrecht, K., Hart, J., Obradovic, Z., Kissinger, C., and Villafranca, J. E. (1998) Protein disorder and the evolution of molecular recognition: Theory, predictions and observations, Pac. Symp. Biocomput. '98, 473-84.
16. Li, X., Romero, P., Rani, M., Dunker, A. K., and Obradovic, Z. (1999) Predicting Protein Disorder for N-, C-, and Internal Regions, Genome Inf. Ser. 10, 30-40.
17. Li, X., Obradovic, Z., Brown, C. J., Garner, E. C., and Dunker, A. K. (2000) Comparing predictors of disordered protein, Genome Inf. Ser. 11, 172-84.
18. Romero, P., Obradovic, Z., Li, X., Garner, E. C., Brown, C. J., and Dunker, A. K. (2001) Sequence complexity of disordered protein, Proteins 42, 38-48.
19. Vucetic, S., Brown, C. J., Dunker, A. K., and Obradovic, Z. (2003) Flavors of protein disorder, Proteins 52, 573-84.
20. Vucetic, S., Radivojac, P., Dunker, A. K., Brown, C. J., and Obradovic, Z. (2001) Methods for improving protein disorder prediction, Proceedings of the International Joint INNS-IEEE Conference on Neural Networks 4, 2718-823.
21. Oldfield, C. J., Cheng, Y., Cortese, M. S., Brown, C. J., Uversky, V. N., and Dunker, A. K. (2005) Comparing and combining predictors of mostly disordered proteins, Biochemistry 44, 1989-2000.
22. Obradovic, Z., Peng, K., Vucetic, S., Radivojac, P., and Dunker, A. K. (2005) Exploiting heterogeneous sequence properties improves prediction of protein disorder, Proteins 61 (Suppl. 7), 176-82.
23. Dunker, A. K., Obradovic, Z., Romero, P., Garner, E. C., and Brown, C. J. (2000) Intrinsic protein disorder in complete genomes, Genome Inf. Ser. 11, 161-71.
24. Iakoucheva, L. M., Brown, C. J., Lawson, J. D., Obradovic, Z., and Dunker, A. K. (2002) Intrinsic disorder in cell-signaling and cancer-associated proteins, J. Mol., Biol. 323, 573-84.
25. Uversky, V. N., Oldfield, C. J., and Dunker, A. K. (2005) Showing your ID: Intrinsic disorder as an ID for recognition, regulation and cell signaling, J. Mol. Recognit. 18, 343-84.
26. Dunker, A. K., Cortese, M. S., Romero, P., Iakoucheva, L. M., and Uversky, V. N. (2005) Flexible nets. The roles of intrinsic disorder in protein interaction networks, FEBS Lett. 272, 5129-48.
27. Demchenko, A. P. (2001) Recognition between flexible protein molecules: Induced and assisted folding, J. Mol. Recognit. 14, 42-61.
28. Dyson, H. J., and Wright, P. E. (2002) Coupling of folding and binding for unstructured proteins, Curr. Opin. Struct. Biol. 12, 54-60.
29. Fuxreiter, M., Simon, I., Friedrich, P., and Tompa, P. (2004) Preformed structural elements feature in partner recognition by intrinsically unstructured proteins, J. Mol. Biol. 338, 1015-26.
30. Dunker, A. K., Brown, C. J., and Obradovic, Z. (2002) Identification and functions of usefully disordered proteins, Adv. Protein Chem. 62, 25-49.
31. Oldfield, C. J., Cheng, Y., Cortese, M. S., Romero, P., Uversky, V. N., and Dunker, A. K. (2005) Coupled folding and binding with α-helix-forming molecular recognition elements, Biochemistry 44, 12454-70.
32. Dyson, H. J., and Wright, P. E. (2005) Intrinsically unstructured proteins and their functions, Nat. Rev. Mol. Cell Biol. 6, 197-208.
33. Fink, A. L. (2005) Natively unfolded proteins, Curr. Opin. Struct. Biol. 15, 35-41.
34. Lee, H., Mok, K. H., Muhandiram, R., Park, K. H., Suk, J. E., Kim, D. H., Chang, J., Sung, Y. C., Choi, K. Y., and Han, K. H. (2000) Local structural elements in the mostly unstructured transcriptional activation domain of human p53, J. Biol. Chem. 275, 29426-32.
35. De Simone, G., Menchise, V., Omaggio, S., Pedone, C., Scozzafava, A., and Supuran, C. T. (2003) Design of weakly basic thrombin inhibitors incorporating novel P1 binding functions: Molecular and X-ray crystallographic studies, Biochemistry 42, 9013-21.
36. Garner, E., Romero, P., Dunker, A. K., Brown, C., and Obradovic, Z. (1999) Predicting Binding Regions within Disordered Proteins, Genome Inf. Ser. 10, 41-50.
37. Adkins, J. N., and Lumb, K. J. (2002) Intrinsic structural disorder and sequence features of the cell cycle inhibitor p57Kip2, Proteins 46, 1-7.
38. Chang, B. S., Minn, A. J., Muchmore, S. W., Fesik, S. W., and Thompson, C. B. (1997) Identification of a novel regulatory domain in Bcl-X(L) and Bcl-2, EMBO J. 16, 968-77.
39. Campbell, K. M., Terrell, A. R., Laybourn, P. J., and Lumb, K. J. (2000) Intrinsic structural disorder of the C-terminal activation domain from the bZIP transcription factor Fos, Biochemistry 39, 2708-13.
40. Sunde, M., McGrath, K. C., Young, L., Matthews, J. M., Chua, E. L., Mackay, J. P., and Death, A. K. (2004) TC-1 is a novel tumorigenic and natively disordered protein associated with thyroid cancer, Cancer Res. 64, 2766-73.
41. Vihinen, M. (1987) Relationship of protein flexibility to thermostability, Protein Eng. 1, 477-80.
42. Kyte, J., and Doolittle, R. F. (1982) A simple method for displaying the hydropathic character of a protein, J. Mol. Biol. 157, 105-32.
43. Efron, B., and Tibshirani, R. (1993) An Introduction to the Bootstrap, Chapman & Hall, New York.
44. Callaghan, A. J., Aurikko, J. P., Ilag, L. L., Grossmann, G. J., Chandran, V., Kuhnel, K., Poljak, L., Carpousis, A. J., Robinson, C. V., Symmons, M. F., and Luisi, B. F. (2004) Studies of the RNA degradosome- organizing domain of the Escherichia coli ribonuclease RNase E, J. Mol. Biol. 340, 965-79.
45. Hartwell, L. H., and Kastan, M. B. (1994) Cell cycle control and cancer, Science 266, 1821-8.
46. Namba, K. (2001) Roles of partly unfolded conformations in macromolecular self-assembly, Genes Cells 6, 1-12.
47. Johnson, L. N., and O'Reilly, M. (1996) Control by phosphorylation, Curr. Opin. Struct. Biol. 6, 762-9.
48. Bailey, R. W., Dunker, A. K., Brown, C. J., Garner, E. C., and Griswold, M. D. (2001) Clusterin, a binding protein with a molten globule-like region, Biochemistry 40, 11828-40.
49. Dunker, A. K., and Rueckert, R. R. (1969) Observations on molecular weight determinations on polyacrylamide gel, J. Biol. Chem. 244, 5074-80.
50. Dunker, A. K., and Kenyon, A. J. (1976) Mobility of sodium dodecyl sulphate-protein complexes, Biochem. J. 153, 191-7.
51. Iakoucheva, L. M., Kimzey, A. L., Masselon, C. D., Smith, R. D., Dunker, A. K., and Ackerman, E. J. (2001) Aberrant mobility phenomena of the DNA repair protein XPA, Protein Sci. 10, 1353-62.
52. Thornton, J. M. (1981) Disulphide bridges in globular proteins, J. Mol. Biol. 151, 261-87.
53. Mohan, A., Radivojac, P., Oldfield, C. J., Vacic, V., Cortese, M. S., Dunker, A. K., and Uversky, V. N. (2006) A dataset of molecular recognition fragments (MoRFs), J. Mol. Biol. (in press).
54. Harvey, R. P., Degryse, E., Stefani, L., Schamber, F., Cazenave, J. P., Courtney, M., Tolstoshev, P., and Lecocq, J. P. (1986) Cloning and expression of a cDNA coding for the anticoagulant hirudin from the bloodsucking leech, Hirudo medicinalis, Proc. Natl. Acad. Sci. U.S.A. 83, 1084-8.
55. Chang, J. Y. (1983) The functional domain of hirudin, a thrombin-specific inhibitor, FEBS Lett. 164, 307-13.
56. Folkers, P. J., Clore, G. M., Driscoll, P. C., Dodt, J., Kohler, S., and Gronenborn, A. M. (1989) Solution structure of recombinant hirudin and the Lys-47 → Glu mutant: A nuclear magnetic resonance and hybrid distance geometry-dynamical simulated annealing study, Biochemistry 28, 2601-17.
57. Maraganore, J. M., Chao, B., Joseph, M. L., Jablonski, J., and Ramachandran, K. L. (1989) Anticoagulant activity of synthetic hirudin peptides, J. Biol. Chem. 264, 8692-8.
58. Stone, S. R., and Hofsteenge, J. (1986) Kinetics of the inhibition of thrombin by hirudin, Biochemistry 25, 4622-8.
59. Doolittle, R. F. (2003) X-ray crystallographic studies on fibrinogen and fibrin, J. Thromb. Haemostasis 1, 1559-65.
60. Doolittle, R. F. (2003) Structural basis of the fibrinogen-fibrin transformation: Contributions from X-ray crystallography, Blood Rev. 17, 33-41.
61. Burgering, M. J., Orbons, L. P., van der Doelen, A., Mulders, J., Theunissen, H. J., Grootenhuis, P. D., Bode, W., Huber, R., and Stubbs, M. T. (1997) The second Kunitz domain of human tissue factor pathway inhibitor: Cloning, structure determination and interaction with factor Xa, J. Mol. Biol. 269, 395-407.
62. Mine, S., Yamazaki, T., Miyata, T., Hara, S., and Kato, H. (2002) Structural mechanism for heparin-binding of the third Kunitz domain of human tissue factor pathway inhibitor, Biochemistry 41, 78-85.
63. Shrive, A. K., Cheetham, G. M., Holden, D., Myles, D. A., Turnell, W. G., Volanakis, J. E., Pepys, M. B., Bloomer, A. C., and Greenhough, T. J. (1996) Three dimensional structure of human C-reactive protein, Nat. Struct. Biol. 3, 346-54.
64. Torphy, T. J. (1998) Phosphodiesterase isozymes: Molecular targets for novel antiasthma agents, Am. J. Respir. Crit. Care Med. 157, 351-70.
65. Gretarsdottir, S., Thorleifsson, G., Reynisdottir, S. T., Manolescu, A., Jonsdottir, S., Jonsdottir, T., Gudmundsdottir, T., Bjarnadottir, S. M., Einarsson, O. B., Gudjonsdottir, H. M., Hawkins, M., Gudmundsson, G., Gudmundsdottir, H., Andrason, H., Gudmundsdottir, A. S., Sigurdardottir, M., Chou, T. T., Nahmias, J., Goss, S., Sveinbjornsdottir, S., Valdimarsson, E. M., Jakobsson, F., Agnarsson, U., Gudnason, V., Thorgeirsson, G., Fingerle, J., Gurney, M., Gudbjartsson, D., Frigge, M. L., Kong, A., Stefansson, K., and Gulcher, J. R. (2003) The gene encoding phosphodiesterase 4D confers risk of ischemic stroke, Nat. Genet. 35, 131-8.
66. Kovala, T., Sanwal, B. D., and Ball, E. H. (1997) Recombinant expression of a type IV, cAMP-specific phosphodiesterase: Characterization and structure-function studies of deletion mutants, Biochemistry 36, 2968-76.
67. Beard, M. B., O'Connell, J. C., Bolger, G. B., and Houslay, M. D. (1999) The unique N-terminal domain of the cAMP phosphodiesterase PDE4D4 allows for interaction with specific SH3 domains, FEBS Lett. 460, 173-7.
68. Hall, C. E., and Slayter, H. S. (1959) The fibrinogen molecule: Its size, shape, and mode of polymerization, J. Biophys. Biochem. Cytol. 5, 11-6.
69. Doolittle, R. F., Everse, S. J., and Spraggon, G. (1996) Human fibrinogen: Anticipating a three-dimensional structure, FASEB J. 10, 1464-70.
70. Bailey, K., Bettelheim, F. R., Lorand, L., and Middlebrook, W. R. (1951) Action of thrombin in the clotting of fibrinogen, Nature 167, 233-4.
71. Ferry, J. D. (1952) The Mechanism of Polymerization of Fibrinogen, Proc. Natl. Acad. Sci. U.S.A. 38, 566-9.
72. Yang, Z., Mochalkin, I., and Doolittle, R. F. (2000) A model of fibrin formation based on crystal structures of fibrinogen and fibrin fragments complexed with synthetic peptides, Proc. Natl. Acad. Sci. U.S.A. 97, 14156-61.
73. Everse, S. J., Spraggon, G., Veerapandian, L., Riley, M., and Doolittle, R. F. (1998) Crystal structure of fragment double-D from human fibrin with two different bound ligands, Biochemistry 37, 8637-42.
74. Tooney, N. M., and Cohen, C. (1972) Microcrystals of a modified fibrinogen, Nature 237, 23-5.
75. Rao, S. P., Poojary, M. D., Elliott, B. W., Jr., Melanson, L. A., Oriel, B., and Cohen, C. (1991) Fibrinogen structure in projection at 18 Å resolution. Electron density by co-ordinated cryo-electron microscopy and X-ray crystallography, J. Mol. Biol. 222, 89-98.
76. Yang, Z., Kollman, J. M., Pandi, L., and Doolittle, R. F. (2001) Crystal structure of native chicken fibrinogen at 2.7 Å resolution, Biochemistry 40, 12515-23.
77. Takagi, T., and Doolittle, R. F. (1975) Amino acid sequence studies on the α chain of human fibrinogen. Location of four plasmin attack points and a covalent cross-linking site, Biochemistry 14, 5149-56.
78. Tsurupa, G., and Medved, L. (2001) Identification and characterization of novel tPA- and plasminogen-binding sites within fibrin(ogen) αC-domains, Biochemistry 40, 801-8.
79. Gorkun, O. V., Henschen-Edman, A. H., Ping, L. F., and Lord, S. T. (1998) Analysis of Aα251 fibrinogen: The αC domain has a role in polymerization, albeit more subtle than anticipated from the analogous proteolytic fragment X, Biochemistry 37, 15434-41.
80. Tompa, P., and Csermely, P. (2004) The role of structural disorder in the function of RNA and protein chaperones, FASEB J. 18, 1169-75.
81. Iakoucheva, L. M., Radivojac, P., Brown, C. J., O'Connor, T. R., Sikes, J. G., Obradovic, Z., and Dunker, A. K. (2004) The importance of intrinsic disorder for protein phosphorylation, Nucleic Acids Res. 32, 1037-49.
82. Fontana, A., Zambonin, M., Polverino de Laureto, P., De Filippis, V., Clementi, A., and Scaramella, E. (1997) Probing the conformational state of apomyoglobin by limited proteolysis, J. Mol. Biol. 266, 223-30.
83. Hubbard, S. J., Eisenmenger, F., and Thornton, J. M. (1994) Modeling studies of the change in conformation required for cleavage of limited proteolytic sites, Protein Sci. 3, 757-68.
84. Receveur-Brechot, V., Bourhis, J. M., Uversky, V. N., Canard, B., and Longhi, S. (2006) Assessing protein disorder and induced folding, Proteins 62, 24-45.
85. Cortese, M. S., Baird, J. P., Uversky, V. N., and Dunker, A. K. (2005) Uncovering the unfoldome: Enriching cell extracts for unstructured proteins by acid treatment, J. Proteome Res. 4, 1610-8.
86. Uversky, V. N. (2003) A rigidifying union: The role of ligands in protein structure and stability, in Recent Research Developments in Biophysics and Biochemistry (Pandalai, S. G., Ed.) pp 711-45, Transworld Research Network, Kerala, India.
87. Romero, P., Zaidi, S., Fang, Y. Y., Uversky, V. N., Radivojac, P., Oldfield, C. J., Cortese, M. S., Sickmeier, M., LeGall, T., Obradovic, Z., and Dunker, A. K. (2006) Alternative splicing in concert with protein intrinsic disorder enables increased functional diversity in multicellular organisms, Proc. Natl. Acad. Sci. U.S.A. 103, 8390-5.
88. Lareau, L. F., Green, R. E., Bhatnagar, R. S., and Brenner, S. E. (2004) The evolving roles of alternative splicing, Curr. Opin. Struct. Biol. 14, 273-82.
89. Stamm, S., Ben-Ari, S., Rafalska, I., Tang, Y., Zhang, Z., Toiber, D., Thanaraj, T. A., and Soreq, H. (2005) Function of alternative splicing, Gene 344, 1-20.
90. Lopez, A. J. (1998) Alternative splicing of pre-mRNA: Developmental consequences and mechanisms of regulation, Annu. Rev. Genet. 32, 279-305.
91. Boue, S., Vingron, M., Kriventseva, E., and Koch, I. (2002) Theoretical analysis of alternative splice forms using computational methods, Bioinformatics 18 (Suppl. 2), S65-73.
92. Xu, X., Yang, D., Ding, J. H., Wang, W., Chu, P. H., Dalton, N. D., Wang, H. Y., Bermingham, J. R., Jr., Ye, Z., Liu, F., Rosenfeld, M. G., Manley, J. L., Ross, J., Jr., Chen, J., Xiao, R. P., Cheng, H., and Fu, X. D. (2005) ASF/SF2-regulated CaMKIIδ alternative splicing temporally reprograms excitation-contraction coupling in cardiac muscle, Cell 120, 59-72.
93. Cochran, A. G. (2000) Antagonists of protein-protein interactions, Chem. Biol. 7, R85-94.
94. Bottger, A., Bottger, V., Sparks, A., Liu, W. L., Howard, S. F., and Lane, D. P. (1997) Design of a synthetic Mdm2-binding mini protein that activates the p53 response in vivo, Curr. Biol. 7, 860-9.
95. Wasylyk, C., Salvi, R., Argentini, M., Dureuil, C., Delumeau, I., Abecassis, J., Debussche, L., and Wasylyk, B. (1999) p53 mediated death of cells overexpressing MDM2 by an inhibitor of MDM2 interaction with p53, Oncogene 18, 1921-34.
96. Chene, P., Fuchs, J., Bohn, J., Garcia-Echeverria, C., Furet, P., and Fabbro, D. (2000) A small synthetic peptide, which inhibits the p53-hdm2 interaction, stimulates the p53 pathway in tumour cell lines, J. Mol. Biol. 299, 245-53.
97. Chene, P. (2004) Inhibition of the p53-MDM2 interaction: Targeting a protein-protein interface, Mol. Cancer Res. 2, 20-8.
98. Vassilev, L. T., Vu, B. T., Graves, B., Carvajal, D., Podlaski, F., Filipovic, Z., Kong, N., Kammlott, U., Lukacs, C., Klein, C., Fotouhi, N., and Liu, E. A. (2004) In vivo activation of the p53 pathway by small-molecule antagonists of MDM2, Science 303, 844-8.
99. Arkin, M. R., and Wells, J. A. (2004) Small-molecule inhibitors of protein-protein interactions: progressing towards the dream, Nat. Rev. Drug Discov. 3, 301-17.
100. Arkin, M. (2005) Protein-protein interactions and cancer: small molecules going in for the kill, Curr. Opin. Chem. Biol. 9, 317-24.
101. Cheng, Y., LeGall, T., Oldfield, C. J., Mueller, J. P., Van, Y. Y., Romero, P., Cortese, M. S., Uversky, V. N., and Dunker, A. K. (2006) Rational drug design via intrinsically disordered protein, Trends Biotechnol. In press.