Journal of Chemical Crystallography

, Volume 41, Issue 4, pp 470–480 | Cite as

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

  • Anna S. Gardberg
  • Brian S. Potter
  • Rex A. Palmer
  • Garry J. McIntyre
  • Dean A. A. Myles


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).


Cyclosporin H Neutron structure Water hydrogens Hydrogen bonding Laue diffraction 



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.


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Copyright information

© Springer Science+Business Media, LLC (outside the USA) 2010

Authors and Affiliations

  • Anna S. Gardberg
    • 1
    • 4
  • Brian S. Potter
    • 2
  • Rex A. Palmer
    • 2
  • Garry J. McIntyre
    • 3
    • 5
  • Dean A. A. Myles
    • 1
  1. 1.Oak Ridge National LaboratoryOak RidgeUSA
  2. 2.School of Crystallography, Birkbeck College, University of LondonLondonUK
  3. 3.Institut Max von Laue–Paul LangevinGrenoble Cedex 9France
  4. 4.Emerald BioStructuresBainbridge IslandUSA
  5. 5.Australian Nuclear Science and Technology OrganisationLucas HeightsAustralia

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