Skip to main content
SpringerLink
Log in

The Neutron Structure of the Formyl Peptide Receptor Antagonist Cyclosporin H (CsH) Unambiguously Determines the Solvent and Hydrogen-Bonding Structure for Crystal Form II

  • ORIGINAL PAPER
  • Published:
Journal of Chemical Crystallography Aims and scope Submit manuscript

Abstract

Single-crystal neutron diffraction data were collected at 20 K to a resolution of 1.05 Å on a crystal of the inverse formyl peptide receptor agonist cyclosporin H, CsH, (crystal form II, CsH-II) on the Laue diffractometer VIVALDI at the Institut Laue-Langevin (Grenoble). The solvent structure and hydrogen bonding network of CsH-II have been unambiguously determined by single-crystal neutron diffraction; the agreement factor R(F 2) is 13.5% for all 2726 reflections. All hydrogen atom positions, including methyl-group orientations, have been determined by crystallographic refinement. The neutron structure of cyclosporin provides unique and complementary insights into methyl orientation, hydrogen-bonding, and solvent interactions that are not available from X-ray analysis alone.

Index Abstract

CsH neutron structure showing the 7 waters and trace of the main chain N1---N11. All water hydrogens were determined experimentally. Thermal ellipsoids are plotted at 85% probability. Drawn with ORTEP-III/RASTER (Burnett and Johnson, Report ORNL-6895, 1996; Merritt and Bacon, Methods in Enzymology 277:505, 1997) as implemented in the program suite WinGX (Farrugia, Journal of Applied Crystallography 32(4):837, 1999) and generated by ORTEP-3 for Windows (Farrugia, Journal of Applied Crystallography 30(5):565, 1997). The main chain trace was drawn with RASMOL (Sayle, Glaxo research and development, 1994).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Ko SY, Dalvit C (1992) Int J Pept Protein Res 40(5):380

    Article  CAS  Google Scholar 

  2. Loosli HR, Kessler H, Oschkinat H, Weber HP, Petcher TJ, Widmer A (1985) Helvetica Chimica Acta 68(3):682

    Article  CAS  Google Scholar 

  3. Altschuh D, Vix O, Rees B, Thierry JC (1992) Science 256(5053):92

    Article  CAS  Google Scholar 

  4. Fesik SW, Gampe RT, Eaton HL, Gemmecker G, Olejniczak ET, Neri P, Holzman TF, Egan DA, Edalji R, Simmer R, Helfrich R, Hochlowski J, Jackson M (1991) Biochemistry 30(26):6574

    Article  CAS  Google Scholar 

  5. Fesik SW, Neri P, Meadows R, Olejniczak ET, Gemmecker G (1992) J Am Chem Soc 114(8):3165

    Article  CAS  Google Scholar 

  6. Kallen J, Mikol V, Taylor P, Walkinshaw MD (1998) J Mol Biol 283(2):435

    Article  CAS  Google Scholar 

  7. Kessler H, Kock M, Wein T, Gehrke M (1990) Helvetica Chimica Acta 73(7):1818

    Article  CAS  Google Scholar 

  8. Knott RB, Schefer J, Schoenborn BP (1990) Acta Crystallogr C Cryst Struct Commun 46:1528

    Article  Google Scholar 

  9. Mikol V, Taylor P, Kallen J, Walkinshaw MD (1998) J Mol Biol 283(2):451

    Article  CAS  Google Scholar 

  10. Weber C, Wider G, von Freyberg B, Traber R, Braun W, Widmer H, Wuthrich K (1991) Biochemistry 30(26):6563

    Article  CAS  Google Scholar 

  11. Wuthrich K, Vonfreyberg B, Weber C, Wider G, Traber R, Widmer H, Braun W (1991) Science 254(5034):953

    Article  CAS  Google Scholar 

  12. Potter B, Palmer RA, Withnall R, Jenkins TC, Chowdhry BZ (2003) Org Biomol Chem 1(9):1466

    Article  CAS  Google Scholar 

  13. McIntyre GJ, Lemée-Cailleau M-H, Wilkinson C (2006) Phys B: Condens Matter 385–386:1055

    Article  Google Scholar 

  14. Wilkinson C, Cowan JA, Myles DAA, Cipriani F, McIntyre GJ (2002) Neutron News 13:37

    Article  Google Scholar 

  15. Campbell JW, Hao Q, Harding MM, Nguti ND, Wilkinson C (1998) J Appl Crystallogr 31(3):496

    Article  CAS  Google Scholar 

  16. Wilkinson C, Khamis HW, Stansfield RFD, McIntyre GJ (1988) J Appl Crystallogr 21:471

    Article  Google Scholar 

  17. Arzt S, Campbell JW, Harding MM, Hao Q, Helliwell JR (1999) J Appl Crystallogr 32(3):554

    Article  CAS  Google Scholar 

  18. Evans PR (2006) Acta Crystallogr D Biol Cryst 62:72–82

    Article  Google Scholar 

  19. Brunger AT (1992) Nature 355(6359):472

    Article  CAS  Google Scholar 

  20. Brunger AT (1997) Methods Enzymol 277:366

    Article  CAS  Google Scholar 

  21. Sheldrick GM (2008) Acta Crystallogr A 64(Pt 1):112

    Article  Google Scholar 

  22. Sears VF (1992) Neutron News 3(3):26

    Article  Google Scholar 

  23. Stegmann C, Seeliger D, Sheldrick G, de Groot B, Wahl M (2009) Angewandte Chemie (International ed. in English)

  24. Sayle R (1994) Glaxo research and development. Greenfield, Middlesex, UK

    Google Scholar 

  25. Vaguine AA, Richelle J, Wodak SJ (1999) Acta Crystallogr D Biol Crystallogr 55(Pt 1):191

    Article  CAS  Google Scholar 

  26. Burnett M, Johnson C (1996) Report ORNL-6895, Oak Ridge National Laboratory, Oak Ridge, TN, USA

  27. Farrugia L (1997) J Appl Crystallogr 30(5):565

    Article  CAS  Google Scholar 

  28. Merritt E, Bacon D (1997) Methods Enzymol 277:505

    Article  CAS  Google Scholar 

  29. Farrugia L (1999) J Appl Crystallogr 32(4):837

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We gratefully acknowledge the ILL for the provision of beamtime. We thank Professor Jon Cooper for his help and interest in the early stages of this study. We thank Ray Simpson for depicting the main chain trace shown in the Index Abstract figure. This research at Oak Ridge National Laboratory’s Center for Structural Molecular Biology (CSMB) was supported by the Office of Biological and Environmental Research, using facilities supported by the US Department of Energy, managed by UT-Battelle, LLC under contract No.DE-AC05-00OR22725. This research was supported in part by an appointment to the ORNL Postdoctoral Research Associates Program at the Oak Ridge National Laboratory, sponsored by the US Department of Energy and administered by the Oak Ridge Institute for Science and Education.

Author information

Author notes

  1. Anna S. Gardberg

    Present address: Emerald BioStructures, 7869 NE Day Rd W Ste 101, Bainbridge Island, WA, 98110, USA

  2. Garry J. McIntyre

    Present address: Australian Nuclear Science and Technology Organisation, New Illawarra Road, Lucas Heights, NSW, Australia

Authors and Affiliations

  1. Oak Ridge National Laboratory, 1 Bethel Valley Road, Oak Ridge, TN 37831-6393, USA

    Anna S. Gardberg & Dean A. A. Myles

  2. School of Crystallography, Birkbeck College, University of London, Malet Street, London, WC1E 7HX, UK

    Brian S. Potter & Rex A. Palmer

  3. Institut Max von Laue–Paul Langevin, 6, rue Jules Horowitz BP 156, 38042, Grenoble Cedex 9, France

    Garry J. McIntyre

Authors
  1. Anna S. Gardberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brian S. Potter
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rex A. Palmer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Garry J. McIntyre
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dean A. A. Myles
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anna S. Gardberg.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gardberg, A.S., Potter, B.S., Palmer, R.A. et al. The Neutron Structure of the Formyl Peptide Receptor Antagonist Cyclosporin H (CsH) Unambiguously Determines the Solvent and Hydrogen-Bonding Structure for Crystal Form II. J Chem Crystallogr 41, 470–480 (2011). https://doi.org/10.1007/s10870-010-9903-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10870-010-9903-7

Keywords

Search

Navigation