Structural and conformational requirements for high-affinity binding to the SH2 domain of Grb21

Journal of Medicinal Chemistry

Volumn 42, Issue 6, 1999, Pages 971-980

  Ettmayer, Peter ^a   France, Dennis ^b   Gounarides, John ^b   Jarosinski, Mark ^d   Martin, Mary Sue ^b   Rondeau, Jean Michel ^c   Sabio, Michael ^b   Topiol, Sid ^b   Weidmann, Beat ^b   Zurini, Mauro ^c   Bair, Kenneth W ^b  

^a Brunnerstra e 59   (Austria)

^b NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

^c NOVARTIS PHARMA AG   (Switzerland)

^d AMGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLO [N ALPHA THIALYSYL O PHOSPHOTYROSYLVALYLASPARAGYLVALYLPROLYL]; CYCLOPEPTIDE; UNCLASSIFIED DRUG;

ARTICLE; BINDING AFFINITY; CATALYSIS; COMPLEX FORMATION; CRYSTALLOGRAPHY; ENZYME ACTIVATION; HYDROGEN BOND; LIGAND BINDING; MOLECULAR MODEL; PROTEIN DOMAIN; PROTON NUCLEAR MAGNETIC RESONANCE; RECEPTOR AFFINITY; RECEPTOR BINDING; STRUCTURE ACTIVITY RELATION;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; CRYSTALLOGRAPHY, X-RAY; ENZYME-LINKED IMMUNOSORBENT ASSAY; GRB2 ADAPTOR PROTEIN; LACTAMS; LIGANDS; MAGNETIC RESONANCE SPECTROSCOPY; MODELS, MOLECULAR; MOLECULAR CONFORMATION; PHOSPHOPEPTIDES; PROTEIN STRUCTURE, SECONDARY; PROTEINS; SRC HOMOLOGY DOMAINS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0033602525     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm9811007     Document Type: Article

References (41)

1. Preliminary report: Ettmayer, P.; France, D.; Gounarides, J.; Jarosinski, M.; Martin, M.-S.; Rondeau, J.-M.; Sabio, M.; Weidmann, B.; Zurini, M.; Bair, K. W. Structural/conformational requirements for high affinity binding to the SH2 domain of Grb2. Proc. Am. Assoc. Cancer Res. 1998, 39, 176 (Abstract #1203).
2. Mayer, B. J.; Gupta, R. Functions of SH2 and SH3 domains. Curr. Top. Microbiol. Immunol. 1998, 228, 1-22. Chook, Y. M.; Gish, G. D.; Kay, C. M.; Pai, E. F.; Pawson, T. The Grb2-mSos1 Complex Binds Phosphopeptides with Higher Affinity than Grb2. J. Biol. Chem. 1996, 271, 30472-30478. Clark, J. W.; Santos-Moore, A.; Stevenson, L. E.; Frackelton, A. R., Jr. Effects of tyrosine kinase inhibitors on the proliferation of human breast cancer cell lines and proteins important in the ras signaling pathway. Int. J. Cancer 1996, 65, 186-191. Ricci, A.; Lanfrancone, L.; Chiari, R.; Belardo, G.; Pertica, C.; Natali, P. G.; Pelicci, P. G.; Segatto, O. Analysis of protein-protein interactions involved in the activation of the Shc/Grb-2 pathway by the ErbB-2 kinase. Oncogene 1995, 11, 1519-1529.
3. Mayer, B. J.; Gupta, R. Functions of SH2 and SH3 domains. Curr. Top. Microbiol. Immunol. 1998, 228, 1-22. Chook, Y. M.; Gish, G. D.; Kay, C. M.; Pai, E. F.; Pawson, T. The Grb2-mSos1 Complex Binds Phosphopeptides with Higher Affinity than Grb2. J. Biol. Chem. 1996, 271, 30472-30478. Clark, J. W.; Santos-Moore, A.; Stevenson, L. E.; Frackelton, A. R., Jr. Effects of tyrosine kinase inhibitors on the proliferation of human breast cancer cell lines and proteins important in the ras signaling pathway. Int. J. Cancer 1996, 65, 186-191. Ricci, A.; Lanfrancone, L.; Chiari, R.; Belardo, G.; Pertica, C.; Natali, P. G.; Pelicci, P. G.; Segatto, O. Analysis of protein-protein interactions involved in the activation of the Shc/Grb-2 pathway by the ErbB-2 kinase. Oncogene 1995, 11, 1519-1529.
4. Mayer, B. J.; Gupta, R. Functions of SH2 and SH3 domains. Curr. Top. Microbiol. Immunol. 1998, 228, 1-22. Chook, Y. M.; Gish, G. D.; Kay, C. M.; Pai, E. F.; Pawson, T. The Grb2-mSos1 Complex Binds Phosphopeptides with Higher Affinity than Grb2. J. Biol. Chem. 1996, 271, 30472-30478. Clark, J. W.; Santos-Moore, A.; Stevenson, L. E.; Frackelton, A. R., Jr. Effects of tyrosine kinase inhibitors on the proliferation of human breast cancer cell lines and proteins important in the ras signaling pathway. Int. J. Cancer 1996, 65, 186-191. Ricci, A.; Lanfrancone, L.; Chiari, R.; Belardo, G.; Pertica, C.; Natali, P. G.; Pelicci, P. G.; Segatto, O. Analysis of protein-protein interactions involved in the activation of the Shc/Grb-2 pathway by the ErbB-2 kinase. Oncogene 1995, 11, 1519-1529.
5. Mayer, B. J.; Gupta, R. Functions of SH2 and SH3 domains. Curr. Top. Microbiol. Immunol. 1998, 228, 1-22. Chook, Y. M.; Gish, G. D.; Kay, C. M.; Pai, E. F.; Pawson, T. The Grb2-mSos1 Complex Binds Phosphopeptides with Higher Affinity than Grb2. J. Biol. Chem. 1996, 271, 30472-30478. Clark, J. W.; Santos-Moore, A.; Stevenson, L. E.; Frackelton, A. R., Jr. Effects of tyrosine kinase inhibitors on the proliferation of human breast cancer cell lines and proteins important in the ras signaling pathway. Int. J. Cancer 1996, 65, 186-191. Ricci, A.; Lanfrancone, L.; Chiari, R.; Belardo, G.; Pertica, C.; Natali, P. G.; Pelicci, P. G.; Segatto, O. Analysis of protein-protein interactions involved in the activation of the Shc/Grb-2 pathway by the ErbB-2 kinase. Oncogene 1995, 11, 1519-1529.
6. Pendergast, A. M.; Quilliam, L. A.; Cripe, L. D.; Bassing, C. H.; Dai, Z.; Li, N.; Batzer, A.; Rabun, K. M.; Der, C. J.; Schlessinger, J. BCR-ABL-induced oncogenesis is mediated by direct interaction with the SH2 domain of the GRB-2 adaptor protein. Cell 1993, 75, 175-185. Tari, A. M.; Arlinghaus, R.; Lopez-Berestein, G. Inhibition of Grb2 and Crk1 proteins results in growth inhibition of Philadelphia chromosome positive leukemic cells. Biochem. Biophys. Res. Commun. 1997, 235, 383-388.
7. Pendergast, A. M.; Quilliam, L. A.; Cripe, L. D.; Bassing, C. H.; Dai, Z.; Li, N.; Batzer, A.; Rabun, K. M.; Der, C. J.; Schlessinger, J. BCR-ABL-induced oncogenesis is mediated by direct interaction with the SH2 domain of the GRB-2 adaptor protein. Cell 1993, 75, 175-185. Tari, A. M.; Arlinghaus, R.; Lopez-Berestein, G. Inhibition of Grb2 and Crk1 proteins results in growth inhibition of Philadelphia chromosome positive leukemic cells. Biochem. Biophys. Res. Commun. 1997, 235, 383-388.
8. Ward, C. W.; Gough, K. H.; Rashke, M.; Wan, S. S.; Tribbick, G.; Wang, J.-X. Systematic mapping of potential binding sites for Shc and Grb2 SH2 domains on insulin receptor substrate-1 and the receptors for insulin, epidermal growth factor, platelet-derived growth factor, and fibroblast growth factor. J. Biol. Chem. 1996, 271, 5603-5609.
9. Jarosinski, M. Unpublished results.
10. Rahuel, J.; Gay, B.; Erdmann, D.; Strauss, A.; García-Echeverria, C.; Furet, P.; Caravatti, G.; Fretz, H.; Schoepfer, J.; Grütter, M. G. Structural basis for specificity of GRB2-SH2 revealed by a novel ligand binding mode. Nature Struct. Biol. 1996, 3, 586.
11. Ogura, K.; Tsuchiya, S.; Terasawa, H.; Yuzawa, S.; Hatanaka, H.; Mandiyan, V.; Schlessinger, J.; Inagaki, F. Conformation of an Shc-derived phosphotyrosine-containing peptide complexed with the Grb2 SH2 domain. J. Biomol. NMR 1997, 10, 273-278.
12. Kuriyan, J.; Cowburn, D. Annu. Rev. Biol. Biophys. Biomol. Struct. 1997, 26, 259-288. For a detailed list of papers reporting about X-ray and NMR structures of ligated SH2 domains, see also ref 20 in ref 21.
13. Marengere, L. E.; Songyang, Z.; Gish, G. D.; Schaller, M. D.; Parsons, J. T.; Stern, M. J.; Cantley, L. W.; Pawson, T. SH2 Domain Specificity and Activity Modified by a Single Residue. Nature 1994, 369, 502-505.
14. Mueller, K.; Gombert, F. O.; Manning, U.; Grossmuller, F.; Graff, P.; Zaegel, H.; Zuber, J. F.; Freuler, F.; Tschopp, C.; Baumann, G. Rapid identification of phosphopeptide ligands for SH2 domains: Screening of peptide libraries by fluorescence-activated bead sorting. J. Biol. Chem. 1996, 271, 16500-16505. Gram, H.; Schmitz, R.; Zuber, J. F.; Baumann, G. Identification of phosphopeptide ligands for the Src-homology 2 (SH2) domain of Grb2 by phage display. Eur. J. Biochem. 1997, 246, 633-637.
15. Mueller, K.; Gombert, F. O.; Manning, U.; Grossmuller, F.; Graff, P.; Zaegel, H.; Zuber, J. F.; Freuler, F.; Tschopp, C.; Baumann, G. Rapid identification of phosphopeptide ligands for SH2 domains: Screening of peptide libraries by fluorescence-activated bead sorting. J. Biol. Chem. 1996, 271, 16500-16505. Gram, H.; Schmitz, R.; Zuber, J. F.; Baumann, G. Identification of phosphopeptide ligands for the Src-homology 2 (SH2) domain of Grb2 by phage display. Eur. J. Biochem. 1997, 246, 633-637.
16. Ligand residues are numbered relative to the position of the phosphotyrosine which is called Y*.
17. Gay, B.; Furet, P.; Garcia-Echeverria, C.; Rahuel, J.; Chene, P.; Fretz, H.; Schoepfer, J.; Caravatti, G. Dual Specificity of Src Homology 2 Domains for Phosphotyrosine Peptide Ligands. Biochemistry 1997, 36, 5712-5718.
18. Distance range constraints (minimal/maximal distance = 2.3/ 3.5 Å, constant = 200, power = 2) between the protein (first atom) and the ligand (second atom): LYS109.N/ASN+2.Oδ1; LEU120.O/ASN+2.Nδ2; LYS109.O/ASN+2.Nδ2; PTY0.O/ VAL+3.N (ligand-to-ligand); SER90.Oγ/PTY0.OP1; SER88.Oγ/ PTY0.OP3;SER88.Oγ/PTY0.OP1;SER96.Oγ/PTY0.OP3;ARG86.NH1/ PTY0.OP3; ARG86.NH2/PTY0.OP2; ARG67.NH1/PTY0.OP2.
19. Zvelebil, M. J. J. M.; Panayotou, G.; Linacre, J.; Waterfield, M. D. Prediction and analysis of SH2 domain - phosphopeptide interactions. Protein Eng. 1995, 8, 527-533.
20. Furet, P.; Gay, B.; Garcia-Echeverria, C.; Rahuel, J.; Fretz, H.; Schoepfer, J.; Caravatti, G. Discovery of 3-Aminobenzyloxycarbonyl as an N-Terminal Group Conferring High Affinity to the Minimal Phosphopeptide Sequence Recognized by the Grb2-SH2 Domain. J. Med. Chem. 1997, 40, 3551-3556.
21. For practical reasons (CPU time), the molecular dynamics simulation was performed only for 50 000 fs in gas phase. To avoid gas-phase artifacts, the protein atoms were kept fixed.
22. Asn was used unprotected. No dehydration of the carboxamide was observed during coupling.
23. Chao, H.-G.; Leiting, B.; Reiss, P. D.; Burkhardt, A. L.; Klimas, C. E.; Bolen, J. B.; Matsueda, G. R. Synthesis and Application of Fmoc-O-[bis(dimethylamino)phosphono]-tyrosine, a Versatile Protected Phosphotyrosine Equivalent. J. Org. Chem. 1995, 60, 7710-7711.
24. Wuthrich, K. NMR of Proteins and Nucleic Acids; Wiley: New York, 1986.
25. McNemar, C.; Snow, M. E.; Windsor, W. T.; Prongay, A.; Mui, P.; Zhang, R.; Durkin, J.; Le, H. V.; Weber, P. C. Thermodynamic and structural analysis of phosphotyrosine polypeptide binding to Grb2-SH2. Biochemistry 1997, 36, 10006-10014.
26. Garcia-Echeverria, C.; Furet, P.; Gay, B.; Fretz, H.; Rahuel, J.; Schoepfer, J.; Caravatti, G. Potent Antagonists of the SH2 Domain of Grb2: Optimization of the X+1 Position of 3-Amino-Z-Tyr(PO3H2)-X+1-Asn-NH2. J. Med. Chem. 1998, 41, 1741-1744.
27. Waksman, G.; Kominos, D.; Robertson, S. C.; Pant, N.; Baltimore, D.; Birge, R. B.; Cowburn, D.; Hanafusa, H.; Mayer, B. J.; Overduin, M.; Resh, M. D.; Rios, C. B.; Silverman, L.; Kuriyan, J. Src-SH2 domain binds phosphopeptides in an extended conformation. Nature 1992, 358, 646-653.
28. Smith, D. B.; Johnson, K. S. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. Gene 1988, 31, 67.
29. Otwinowski, Z.; Minor, W. Processing of X-ray Diffraction Data Collected in Oscillation Mode. Methods in Enzymology; Academic Press: New York, 1996; p 276.
30. Navaza, J. AMoRe: an Automated Package for Molecular Replacement. Acta Crystallogr. 1994, A50, 157-163.
31. Brünger, A. T. X-PLOR, Version 3.1: A System for Crystallography and NMR; Yale University Press: New Haven, CT, 1992.
32. Engh, R. A.; Huber, R. Accurate Bond and Angle Parameters for X-ray Protein Structure Refinement. Acta Crystallogr. 1994, A47, 392-400.
33. Sybyl (v. 6.5); Tripos, Inc., 1699 S. Hanley Rd, St. Louis, MO 63144-2913.
34. Gasteiger, J.; Marsili, M. Iterative partial equalization of orbital electronegativity - a rapid access to atomic charges. Tetrahedron 1980, 36, 3219-3228.
35. Rance, M.; Soerensen, O. W.; Bodenhausen, G.; Wagner G.; Ernst, R. R.; Wuethrich, K. Improved spectral resolution in COSY proton NMR spectra of proteins via double quantum filtering. Biochem. Biophys. Res. Commun. 1983, 117, 479-485.
36. Bax, A.; Davis, D. G. Practical aspects of two-dimensional transverse NOE spectroscopy. J. Magn. Reson. 1985, 63, 207-213.
37. Marion, D.; Wuethrich, K. Application of phase sensitive two-dimensional correlated spectroscopy (COSY) for measurements of proton-proton spin-spin coupling constants in proteins. Biochem. Biophys. Res. Commun. 1983, 113, 967-974.
38. Sieber, P. An improved method for anchoring of 9-fluorenylmethoxycarbonyl amino acids to 4-alkoxybenzyl alcohol resins. Tetrahedron Lett. 1987, 28, 6147-6150.
39. Hermann, P.; Stalla, K.; Schwimmer, J.; Willhardt, I.; Kutschera, I. Synthesis of some sulfur-containing amino acid analogues. J. Prakt. Chem. 1969, 311, 1018-1028.
40. Tam, J. P.; Wu, C. R.; Liu, W.; Zhang, J. W. Disulfide bond formation in peptides by dimethyl sulfoxide. Scope and applications. J. Am. Chem. Soc. 1991, 113, 6657-6662.
41. Kaiser, E.; Colescott, R. L.; Bossinger, C. D.; Cook, P. I. Color test for detection of free terminal amino groups in the solid-phase synthesis of peptides. Anal. Biochem. 1970, 34, 595-598.