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The structure of malaria pigment β-haematin

Nature volume 404, pages 307–310 (2000)Cite this article

Abstract

Despite the worldwide public health impact of malaria, neither the mechanism by which the Plasmodium parasite detoxifies and sequesters haem, nor the action of current antimalarial drugs is well understood. The haem groups released from the digestion of the haemoglobin of infected red blood cells are aggregated into an insoluble material called haemozoin or malaria pigment. Synthetic β-haematin (FeIII-protoporphyrin-IX)2 is chemically1,2, spectroscopically2,3 and crystallographically4 identical to haemozoin and is believed to consist of strands of FeIII-porphyrin units, linked into a polymer by propionate oxygen-iron bonds. Here we report the crystal structure of β-haematin determined using simulated annealing techniques to analyse powder diffraction data obtained with synchrotron radiation. The molecules are linked into dimers through reciprocal iron–carboxylate bonds to one of the propionic side chains of each porphyrin, and the dimers form chains linked by hydrogen bonds in the crystal. This result has implications for understanding the action of current antimalarial drugs and possibly for the design of new therapeutic agents.

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Figure 1: Representation of the FeIII-protoporphyrin-IX molecule used in the structure solution (hydrogen atoms not shown).
Figure 2: Two unit cells of the crystal structure of β-haematin, viewed along the [001] direction.
Figure 3: Observed (crosses) and calculated (solid line) X-ray powder diffraction patterns of β-haematin, using X-rays of wavelength 1.16192 Å.
Figure 4: Packing diagram of the crystal structure of β-haematin.

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Acknowledgements

The National Synchrotron Light Source, Brookhaven National Laboratory, is supported by the US Department of Energy, Division of Chemical Sciences and Division of Materials Sciences. D.S.B. acknowledges financial support from Dreyfus Foundation and the United Nations Development Programs/World Bank/World Health Organisation Special Programme for Research and Training in Tropical Diseases. The SUNY X3 beamline at the National Synchrotron Light Source is supported by the Division of Basic Energy Sciences of the US Department of Energy.

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Author notes

  1. Sara K. Madsen

    Present address: Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, Minnesota, 48109, USA

Authors and Affiliations

  1. Department of Physics & Astronomy State University of New York, Stony Brook, 11794-3800, New York, USA

    Silvina Pagola & Peter W. Stephens

  2. Department of Chemistry, University of Wyoming, Laramie, 82071-3838, Wyoming, USA

    D. Scott Bohle, Andrew D. Kosar & Sara K. Madsen

Authors
  1. Silvina Pagola
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Corresponding author

Correspondence to Peter W. Stephens.

Supplementary information

41586_2000_BF35005132_MOESM1_ESM.doc

(a) atomic positions after the Rietveld refinement, (b) selected interatomic distances and (c) selected interatomic angles.

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Pagola, S., Stephens, P., Bohle, D. et al. The structure of malaria pigment β-haematin. Nature 404, 307–310 (2000). https://doi.org/10.1038/35005132

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