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Structural and conformational requirements for high-affinity binding to the SH2 domain of Grb2(1).

Ettmayer P, France D, Gounarides J, Jarosinski M, Martin MS, Rondeau JM, Sabio M, Topiol S, Weidmann B, Zurini M, Bair KW
J Med Chem 42 971-80 (1999)
Cited: 52 times
EuropePMC logo PMID: 10090780

Abstract

Following earlier work on cystine-bridged peptides, cyclic phosphopeptides containing nonreducible mimics of cystine were synthesized that show high affinity and specificity toward the Src homology (SH2) domain of the growth factor receptor-binding protein (Grb2). Replacement of the cystine in the cyclic heptapeptide cyclo(CYVNVPC) by D-alpha-acetylthialysine or D-alpha-lysine gave cyclo(YVNVP(D-alpha-acetyl-thiaK)) (22) and cyclo(YVNVP(D-alpha-acetyl-K)) (30), which showed improved binding 10-fold relative to that of the control peptide KPFYVNVEF (1). NMR spectroscopy and molecular modeling experiments indicate that a beta-turn conformation centered around YVNV is essential for high-affinity binding. X-ray structure analyses show that the linear peptide 1 and the cyclic compound 21 adopt a similar binding mode with a beta-turn conformation. Our data confirm the unique structural requirements of the ligand binding site of the SH2 domain of Grb2. Moreover, the potency of our cyclic lactams can be explained by the stabilization of the beta-turn conformation by three intramolecular hydrogen bonds (one mediated by an H2O molecule). These stable and easily accessible cyclic peptides can serve as templates for the evaluation of phosphotyrosine surrogates and further chemical elaboration.

Articles - 1bm2 mentioned but not cited (4)

  1. Insights into equilibrium dynamics of proteins from comparison of NMR and X-ray data with computational predictions. Yang LW, Eyal E, Chennubhotla C, Jee J, Gronenborn AM, Bahar I. Structure 15 741-749 (2007)
  2. Binding modes of peptidomimetics designed to inhibit STAT3. Dhanik A, McMurray JS, Kavraki LE. PLoS One 7 e51603 (2012)
  3. High resolution crystal structure of the Grb2 SH2 domain with a phosphopeptide derived from CD28. Higo K, Ikura T, Oda M, Morii H, Takahashi J, Abe R, Ito N. PLoS One 8 e74482 (2013)
  4. Secondary structure, a missing component of sequence-based minimotif definitions. Sargeant DP, Gryk MR, Maciejewski MW, Thapar V, Kundeti V, Rajasekaran S, Romero P, Dunker K, Li SC, Kaneko T, Schiller MR. PLoS One 7 e49957 (2012)


Reviews citing this publication (6)

  1. Correlating structure and energetics in protein-ligand interactions: paradigms and paradoxes. Martin SF, Clements JH. Annu Rev Biochem 82 267-293 (2013)
  2. Peptides with anticancer use or potential. Janin YL. Amino Acids 25 1-40 (2003)
  3. The synthesis of phosphopeptides. McMurray JS, Coleman DR, Wang W, Campbell ML. Biopolymers 60 3-31 (2001)
  4. Grb2 SH2 domain-binding peptide analogs as potential anticancer agents. Lung FD, Tsai JY. Biopolymers 71 132-140 (2003)
  5. Targeting kinase signaling pathways with constrained peptide scaffolds. Hanold LE, Fulton MD, Kennedy EJ. Pharmacol Ther 173 159-170 (2017)
  6. Structural conservation of a short, functional, peptide-sequence motif. Fox-Erlich S, Schiller MR, Gryk MR. Front Biosci (Landmark Ed) 14 1143-1151 (2009)

Articles citing this publication (42)

  1. Crystal structures of the SH2 domain of Grb2: highlight on the binding of a new high-affinity inhibitor. Nioche P, Liu WQ, Broutin I, Charbonnier F, Latreille MT, Vidal M, Roques B, Garbay C, Ducruix A. J Mol Biol 315 1167-1177 (2002)
  2. GRID: a novel Grb-2-related adapter protein that interacts with the activated T cell costimulatory receptor CD28. Ellis JH, Ashman C, Burden MN, Kilpatrick KE, Morse MA, Hamblin PA. J Immunol 164 5805-5814 (2000)
  3. Conformational constraint in protein ligand design and the inconsistency of binding entropy. Udugamasooriya DG, Spaller MR. Biopolymers 89 653-667 (2008)
  4. Functional Analysis of Human Hub Proteins and Their Interactors Involved in the Intrinsic Disorder-Enriched Interactions. Hu G, Wu Z, Uversky VN, Kurgan L. Int J Mol Sci 18 E2761 (2017)
  5. NetTurnP--neural network prediction of beta-turns by use of evolutionary information and predicted protein sequence features. Petersen B, Lundegaard C, Petersen TN. PLoS One 5 e15079 (2010)
  6. Thermodynamic and Structural Effects of Macrocyclization as a Constraining Method in Protein-Ligand Interactions. Delorbe JE, Clements JH, Whiddon BB, Martin SF. ACS Med Chem Lett 1 448-452 (2010)
  7. Coupled motions in the SH2 and kinase domains of Csk control Src phosphorylation. Wong L, Lieser SA, Miyashita O, Miller M, Tasken K, Onuchic JN, Adams JA, Woods VL, Jennings PA. J Mol Biol 351 131-143 (2005)
  8. Conformationally constrained peptidomimetic inhibitors of signal transducer and activator of transcription. 3: Evaluation and molecular modeling. Mandal PK, Limbrick D, Coleman DR, Dyer GA, Ren Z, Birtwistle JS, Xiong C, Chen X, Briggs JM, McMurray JS. J Med Chem 52 2429-2442 (2009)
  9. Grb7 SH2 domain structure and interactions with a cyclic peptide inhibitor of cancer cell migration and proliferation. Porter CJ, Matthews JM, Mackay JP, Pursglove SE, Schmidberger JW, Leedman PJ, Pero SC, Krag DN, Wilce MC, Wilce JA. BMC Struct Biol 7 58 (2007)
  10. Sequence, structure and energetic determinants of phosphopeptide selectivity of SH2 domains. Sheinerman FB, Al-Lazikani B, Honig B. J Mol Biol 334 823-841 (2003)
  11. Ligand preorganization may be accompanied by entropic penalties in protein-ligand interactions. Benfield AP, Teresk MG, Plake HR, DeLorbe JE, Millspaugh LE, Martin SF. Angew Chem Int Ed Engl 45 6830-6835 (2006)
  12. Quantitative relation between intermolecular and intramolecular binding of pro-rich peptides to SH3 domains. Zhou HX. Biophys J 91 3170-3181 (2006)
  13. Structural and energetic aspects of Grb2-SH2 domain-swapping. Benfield AP, Whiddon BB, Clements JH, Martin SF. Arch Biochem Biophys 462 47-53 (2007)
  14. Structural basis for differential recognition of tyrosine-phosphorylated sites in the linker for activation of T cells (LAT) by the adaptor Gads. Cho S, Velikovsky CA, Swaminathan CP, Houtman JC, Samelson LE, Mariuzza RA. EMBO J 23 1441-1451 (2004)
  15. Structural basis for the binding of high affinity phosphopeptides to Stat3. McMurray JS. Biopolymers 90 69-79 (2008)
  16. Significant compensatory role of position Y-2 conferring high affinity to non-phosphorylated inhibitors of Grb2-SH2 domain. Long YQ, Voigt JH, Lung FD, King CR, Roller PP. Bioorg Med Chem Lett 9 2267-2272 (1999)
  17. High-Affinity Interactions of the nSH3/cSH3 Domains of Grb2 with the C-Terminal Proline-Rich Domain of SOS1. Liao TJ, Jang H, Nussinov R, Fushman D. J Am Chem Soc 142 3401-3411 (2020)
  18. Structural requirements for Tyr in the consensus sequence Y-E-N of a novel nonphosphorylated inhibitor to the Grb2-SH2 domain. Long YQ, Yao ZJ, Voigt JH, Lung FD, Luo JH, Burke TR, King CR, Yang D, Roller PP. Biochem Biophys Res Commun 264 902-908 (1999)
  19. Development of Grb2 SH2 Domain Signaling Antagonists: A Potential New Class of Antiproliferative Agents. Burke TR. Int J Pept Res Ther 12 33-48 (2006)
  20. Evaluation of macrocyclic Grb2 SH2 domain-binding peptide mimetics prepared by ring-closing metathesis of C-terminal allylglycines with an N-terminal beta-vinyl-substituted phosphotyrosyl mimetic. Oishi S, Karki RG, Shi ZD, Worthy KM, Bindu L, Chertov O, Esposito D, Frank P, Gillette WK, Maderia M, Hartley J, Nicklaus MC, Barchi JJ, Fisher RJ, Burke TR. Bioorg Med Chem 13 2431-2438 (2005)
  21. Ring-closing metathesis of C-terminal allylglycine residues with an N-terminal beta-vinyl-substituted phosphotyrosyl mimetic as an approach to novel Grb2 SH2 domain-binding macrocycles. Oishi S, Shi ZD, Worthy KM, Bindu LK, Fisher RJ, Burke TR. Chembiochem 6 668-674 (2005)
  22. Crystal structures of a high-affinity macrocyclic peptide mimetic in complex with the Grb2 SH2 domain. Phan J, Shi ZD, Burke TR, Waugh DS. J Mol Biol 353 104-115 (2005)
  23. Bent Into Shape: Folded Peptides to Mimic Protein Structure and Modulate Protein Function. Merritt HI, Sawyer N, Arora PS. Pept Sci (Hoboken) 112 e24145 (2020)
  24. Global optimization of conformational constraint on non-phosphorylated cyclic peptide antagonists of the Grb2-SH2 domain. Long YQ, Lung FD, Roller PP. Bioorg Med Chem 11 3929-3936 (2003)
  25. N-terminal carboxyl and tetrazole-containing amides as adjuvants to Grb2 SH2 domain ligand binding. Burke TR, Yao ZJ, Gao Y, Wu JX, Zhu X, Luo JH, Guo R, Yang D. Bioorg Med Chem 9 1439-1445 (2001)
  26. Percentile-based spread: a more accurate way to compare crystallographic models. Pozharski E. Acta Crystallogr D Biol Crystallogr 66 970-978 (2010)
  27. Structure-based design of thioether-bridged cyclic phosphopeptides binding to Grb2-SH2 domain. Li P, Peach ML, Zhang M, Liu H, Yang D, Nicklaus M, Roller PP. Bioorg Med Chem Lett 13 895-899 (2003)
  28. Design and synthesis of backbone cyclic phosphorylated peptides: The IkappaB model. Qvit N, Hatzubai A, Shalev DE, Friedler A, Ben-Neriah Y, Gilon C. Biopolymers 91 157-168 (2009)
  29. SOS1 interacts with Grb2 through regions that induce closed nSH3 conformations. Liao TJ, Jang H, Fushman D, Nussinov R. J Chem Phys 153 045106 (2020)
  30. Structure-based design of potent Grb2-SH2 domain antagonists not relying on phosphotyrosine mimics. Jiang S, Li P, Peach ML, Bindu L, Worthy KW, Fisher RJ, Burke TR, Nicklaus M, Roller PP. Biochem Biophys Res Commun 349 497-503 (2006)
  31. Photochemical Z-->E isomerization of a hemithioindigo/hemistilbene omega-amino acid. Cordes T, Heinz B, Regner N, Hoppmann C, Schrader TE, Summerer W, Rück-Braun K, Zinth W. Chemphyschem 8 1713-1721 (2007)
  32. Microwave-assisted synthesis of cyclic phosphopeptide on solid support. Qvit N. Chem Biol Drug Des 85 300-305 (2015)
  33. Small nonphosphorylated Grb2-SH2 domain antagonists evaluated by surface plasmon resonance technology. Lung FD, Chang CW, Chong MC, Liou CC, Li P, Peach ML, Nicklaus MC, Lou BS, Roller PP. Biopolymers 80 628-635 (2005)
  34. Multi-photon excitation of intrinsic protein fluorescence and its application to pharmaceutical drug screening. Buehler C, Dreessen J, Mueller K, So PT, Schilb A, Hassiepen U, Stoeckli KA, Auer M. Assay Drug Dev Technol 3 155-167 (2005)
  35. Structural basis for a novel interaction between TXNIP and Vav2. Liu S, Wu X, Zong M, Tempel W, Loppnau P, Liu Y. FEBS Lett 590 857-865 (2016)
  36. Utilization of 3'-carboxy-containing tyrosine derivatives as a new class of phosphotyrosyl mimetics in the preparation of novel non-phosphorylated cyclic peptide inhibitors of the Grb2-SH2 domain. Song YL, Tan J, Luo XM, Long YQ. Org Biomol Chem 4 659-666 (2006)
  37. A conformationally fixed analog of the peptide mimic Grb2-SH2 domain: synthesis and evaluation against the A431 cancer cell. Iwata T, Tanaka K, Tahara T, Nozaki S, Onoe H, Watanabe Y, Fukase K. Mol Biosyst 9 1019-1025 (2013)
  38. GRB2 dimerization mediated by SH2 domain-swapping is critical for T cell signaling and cytokine production. Sandouk A, Xu Z, Baruah S, Tremblay M, Hopkins JB, Chakravarthy S, Gakhar L, Schnicker NJ, Houtman JCD. Sci Rep 13 3505 (2023)
  39. Synthesis and structural characterization of a monocarboxylic inhibitor for GRB2 SH2 domain. Xiao T, Sun L, Zhang M, Li Z, Haura EB, Schonbrunn E, Ji H. Bioorg Med Chem Lett 51 128354 (2021)
  40. The relative binding position of Nck and Grb2 adaptors impacts actin-based motility of Vaccinia virus. Basant A, Way M. Elife 11 e74655 (2022)
  41. Apparent instability of crystallographic refinement in the presence of disordered model fragments and upon insufficiently restrained model geometry. Pozharski E. Acta Crystallogr D Biol Crystallogr 67 966-972 (2011)
  42. Design and synthesis of a beta-amino phosphotyrosyl mimetic suitably protected for peptide synthesis. Lee K, Zhang M, Yang D, Burke TR. Bioorg Med Chem Lett 12 3399-3401 (2002)


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