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Structure determination of racemic trichogin A IV using centrosymmetric crystals

Nature Structural Biology volume 1, pages 908–914 (1994)Cite this article

Abstract

Direct methods of crystal structure solution are greatly facilitated in centrosymmetric space groups where the complexity of the phase-problem is reduced. For most peptides and proteins, crystallization in a centrosymmetric arrangement is precluded by an intrinsic dissymmetry due to the constituent chiral amino acid residues. The synthetic accessibility of peptide sequences containing amino acids of either chirality offers the possibility for co crystallization of racemic crystals. We report here the first use of such an approach for the de novo structure determination of a medium-sized molecule, trichogin A IV, which is a constituent of a fungal lipopeptaibol mixture possessing membrane-modifying properties of biological interest.

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References

  1. Moffat, A.S. New methods make mid-sized molecules easier to solve. Science 256, 309–310 (1992).

    Article  CAS  Google Scholar 

  2. Karle, J. & Hauptman, H. A theory of phase determination for the four types of non- entrosymmetric space groups 1P2221, 2P221, 3P121, 3P22. Acta crystallogr 9, 635–651 (1956).

    Article  CAS  Google Scholar 

  3. Shiono, M. & Woolfson, M.M. Direct-space methods in phase extension and phase determination. I. Low-density elimination. Acta crystallogr. A48, 451–456 (1992).

    Article  Google Scholar 

  4. DeTitta, G.T., Weeks, C.M., Thuman, P., Miller, R. & Hauptman, H. Structure solution by minimal-function phase refinement and Fourierfiltering. I. Theoretical Basis. Acta crystallogr. A50, 203–210 (1994).

    Article  CAS  Google Scholar 

  5. Weeks, C.M., DeTitta, G.T., Hauptman, H.A., Thuman, P. & Miller, R. Structure solution by minimal-function phase refinement and Fourier filtering. II. Implementation and Applications. Acta crystallogr. A50, 210–220 (1994).

    Article  CAS  Google Scholar 

  6. Langs, D.A. Three-dimensional structure at 0.86Å of the uncomplexed form of the transmembrane ion channel peptide Gramicidin A. Science 241, 188–191 (1988).

    Article  CAS  Google Scholar 

  7. Glover, I., Haneef, I., Pitts, J., Wood, S., Moss, T., Tickle, I. & Blundell, T. Conformational flexibility in a small globular hormone: X-ray analysis of avian pancreatic polypeptide at 0.98 Å resolution. Biopolymers 22, 293–304 (1983).

    Article  CAS  Google Scholar 

  8. Karle, I.L., Karle, J., Mastropaolo, D., Camerman, A. & Camerman, N. [Leu 5] enkephalin: Four cocrystallizing conformers with extended backbones that form an antiparallel β-sheet. Acta. crystallogr. B39, 625–637 (1983).

    Article  CAS  Google Scholar 

  9. Mackay, A.L. Crystal enigma. Nature 342, 133 (1989).

    Article  Google Scholar 

  10. Jacques, J., Collet, A. & Wilen, S.H. in Enantiomers, racemates and resolutions (John Wiley & Sons, New York; 1981).

    Google Scholar 

  11. Brock, C.P., Schweizer, W.B. & Dunitz, J.C. On the validity of Wallach's rule: On the density and stability of racemic crystals compared with their chiral counterparts. J. Am. chem. Soc. 113, 9811–9820 (1992).

    Article  Google Scholar 

  12. Zawadke, L.E. & Berg, J.E. The structure of a centrosymmetric protein crystal. Prot. Struct. Funct. Genet. 16, 301–305 (1993).

    Article  Google Scholar 

  13. Doi, M. et al. Structural characteristics of enantiomorphic DNA:Crystal analysis of racemates of the d(CGCGCG) duplex. J. Am. chem. Soc. 115, 10432–10433 (1993).

    Article  CAS  Google Scholar 

  14. Doi, M., Ishibe, A., Shinozaki, H., Urata, H., Inoue, M. & Ishida, T. Conserved and novel structural characteristics of enantiomorphic Leu-enkephalin. Int. J. Peptide Prot. Res. 43, 325–331 (1994).

    Article  CAS  Google Scholar 

  15. Benedetti, E. et al. Peptaibol antibiotics: A study on the helical structure of the 2–9 sequence of Emerimicins III and IV. Proc. natn. Acad. Sci. U.S.A. 79, 7951–7954 (1982).

    Article  CAS  Google Scholar 

  16. Bruckner, H., Cussin, C. & Kripp, T. Detection of new peptaibol antibiotics (mycotoxins) in species and strains of the fungal genus Trichoderma . in Peptides: chemistry and biology, 650–652 (ed. Marshall, G.R. ESCOM Science Publishers, Leiden, The Netherlands; 1988).

    Chapter  Google Scholar 

  17. Pandey, R.C., Cook, J.C., Jr & Rinehart, K.L. High resolution and field desorption mass spectrometry studies and revised structures of Alamethicins I and II. J. Am. chem. Soc. 99, 8469–8483 (1977).

    Article  CAS  Google Scholar 

  18. Fox, R.O. & Richards, F.M. A voltage-gated ion channel model inferred from the crystal structure of Alamethicin at 1.5Å resolution. Nature, 300, 325–330 (1982).

    Article  CAS  Google Scholar 

  19. Rinehart, K.L., et al. Structures of eleven zervamicin and two emerimicin peptide antibiotics studied by fast atom bombardment mass spectrometry. J. Am. chem. Soc. 103, 6517–6520 (1981).

    Article  CAS  Google Scholar 

  20. Karle, I.L., Flippen-Anderson, J.L., Agarwalla, S. & Balaram, P. Crystal structure of [Leu1] Zervamicin, a membrane ion channel peptide: Implications for gating mechanisms. Proc. natn. Acad. Sci. U.S.A. 88, 5307–5311 (1991).

    Article  CAS  Google Scholar 

  21. Pandey, R.C., Meng, H., Cook, J.C., Jr. & Rinehart, K.L., Jr. Structure of antiamoebin I from high resolution field desorption and gas chromatographic mass spectrometry studies. J. Am. chem. Soc. 99, 5203–5205 (1977).

    Article  CAS  Google Scholar 

  22. Das, K.M., Ragothama, S., Balaram, P., Membrane channel forming polypeptides. Molecular conformation and mitochondrial uncoupling activity of Antiamoebin, an α-aminoisobutyric acid containing peptide. Biochemistry 25, 7110–7117 (1986).

    Article  CAS  Google Scholar 

  23. Auvin-Guette, C., Rebuffat, S., Prigent, Y. & Bodo, B. Trichogin A IV, an 11-residue lipopeptaibol from Trichoderma longibrachiatum . J. Am. chem. Soc. 114, 2170–2174 (1992).

    Article  CAS  Google Scholar 

  24. Karle, I.L., Sukumar, M. & Balaram, P. Parallel packing of α-helices in crystals of the Zervamicin IIA analog Boc-Trp-Ile-Ala-Aib-Ile-Val-Aib-Leu-Aib-Pro-OMe. 2H2O. Proc. natn. Acad. Sci. U.S.A. 83, 9284–9288 (1986).

    Article  CAS  Google Scholar 

  25. Bosch, R., Jung, G., Schmitt, H. & Winter, W. Crystal structure of the α-helical undecapeptide Boc-L-Ala-Aib-Ala-Aib-Ala-Glu(OBzl)-Ala-Aib-Ala-Aib-Ala-OMe. Biopolymers 26, 961–978 (1985).

    Article  Google Scholar 

  26. Presta, L.G. & Rose, G.D. Helix signals in proteins. Science 240, 1632–1641 (1988).

    Article  CAS  Google Scholar 

  27. Zhou, H.X., Lyu, P.C., Wemmer, D.E. & Kallenbach, N.R. Structure of a C-terminal α-helix cap in a synthetic peptide. J. Am. chem. Soc. 116, 1139–1140 (1994).

    Article  CAS  Google Scholar 

  28. Toniolo, C. & Benedetti, E. The polypeptide 310-helix. Trends biochem. Sci. 16, 350–353 (1991).

    Article  CAS  Google Scholar 

  29. Nagaraj, R. & Balaram, P. Alamethicin, a transmembrane channel. Accs. chem. Res. 14, 356–362 (1981).

    Article  CAS  Google Scholar 

  30. Karle, I.L. Folding, aggregation and molecular recognition in peptides. Acta crystallogr. B48, 341–356 (1992).

    Article  CAS  Google Scholar 

  31. Bodo, B. et al. Synthesis and membrane-modifying properties of analogues of the lipopeptaibol Trichogin A IV with variable Nα-acyl chain length. in Peptides 1994. (ed. Maia, H.L.S.) (ESCOM Science Publisher, Leiden, The Netherlands, 1995).

    Google Scholar 

  32. Menestrina, G., Voges, K.-P., Jung, G. & Boheim, G. Voltage-dependent channel formation by rods of helical polypeptides. J. memb. Biol. 93, 111–132 (1986).

    Article  CAS  Google Scholar 

  33. Cosson, P. & Bonifacino, J.S. Role of transmembrane domain interactions in the assembly of class II MHC molecules. Science 258, 659–662 (1992).

    Article  CAS  Google Scholar 

  34. Walker, N. & Stuart, D. An empirical method for correcting diffractometer data for absorption effects. Acta crystallogr. A39, 158–166 (1983).

    Article  CAS  Google Scholar 

  35. Sheldrick, G.M. in Crystallographic Computing 3 eds Sheldrick, G.M., Kruger, C. & Goddard, R. 175–189 (Oxford University Press: England, 1985).

    Google Scholar 

  36. Enraf Nonius Structure Determination Package. (Enraf Nonius, Delft, The Netherlands, 1979).

  37. IUPAC-IUB Commission on Biochemical Nomenclature, Abbreviations and symbols for the description of the conformation of polypeptide chains. Biochemistry 9, 3471–3479 (1970).

    Article  Google Scholar 

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Authors and Affiliations

  1. Biopolymer Research Center, C.N.R., Department of Organic Chemistry, University of Padova, 35131, Padova, Italy

    Claudio Toniolo, Cristina Peggion, Marco Crisma & Fernando Formaggio

  2. SmithKline Beecham Pharmaceuticals, P.O. Box 1539, UW-2950, King of Prussia, Pennsylvania, 19406, USA

    Xiuqi Shui & Drake S. Eggleston

Authors
  1. Claudio Toniolo
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  2. Cristina Peggion
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  3. Marco Crisma
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  4. Fernando Formaggio
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  5. Xiuqi Shui
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  6. Drake S. Eggleston
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Toniolo, C., Peggion, C., Crisma, M. et al. Structure determination of racemic trichogin A IV using centrosymmetric crystals. Nat Struct Mol Biol 1, 908–914 (1994). https://doi.org/10.1038/nsb1294-908

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