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Mouse and human indoleamine 2,3-dioxygenase display some distinct biochemical and structural properties

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Abstract

The hemoprotein indoleamine 2,3-dioxygenase (IDO) is the first and rate-limiting enzyme in the most significant pathway for mammalian tryptophan metabolism. It has received considerable attention in recent years, particularly due to its dual role in immunity and the pathogenesis of many diseases. Reported here are differences and similarities between biochemical behaviour and structural features of recombinant human IDO and recombinant mouse IDO. Significant differences were observed in the conversion of substrates and pH stability. Differences in inhibitor potency and thermal stability were also noted. Secondary structural features were broadly similar but variation between species was apparent, particularly in the α-helix portion of the enzymes. With mouse models substituting for human diseases, the differences between mouse and human IDO must be recognised before applying experimental findings from one system to the next.

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Acknowledgments

This work was supported by the Australian Research Council and the Sir Zelman Cowen Universities Fund.

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Authors and Affiliations

  1. Molecular Immunopathology Unit, Bosch Institute, University of Sydney, Sydney, Australia

    Christopher J. D. Austin, Florian Astelbauer, Helen J. Ball & Nicholas H. Hunt

  2. Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, Australia

    Priambudi Kosim-Satyaputra, Robert D. Willows & Joanne F. Jamie

Authors
  1. Christopher J. D. Austin
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  2. Florian Astelbauer
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  3. Priambudi Kosim-Satyaputra
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  4. Helen J. Ball
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  5. Robert D. Willows
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  6. Joanne F. Jamie
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  7. Nicholas H. Hunt
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Correspondence to Christopher J. D. Austin.

Electronic supplementary material

Figure (a)–(c): Substrate concentration versus turnover rate (V) in μmoles of kynurenine produced per mg of protein.

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Figure b (TIF 116 kb)

Figure c (TIF 119 kb)

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Austin, C.J.D., Astelbauer, F., Kosim-Satyaputra, P. et al. Mouse and human indoleamine 2,3-dioxygenase display some distinct biochemical and structural properties. Amino Acids 36, 99–106 (2009). https://doi.org/10.1007/s00726-008-0037-6

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  • DOI: https://doi.org/10.1007/s00726-008-0037-6

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