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A structural and computational study of citrulline in biochemical reactions

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Abstract

Citrulline, a non-essential amino acid, is used therapeutically in mitochondrial diseases, especially since it is a well-tolerated medicinal compound. Athletes use citrulline to enhance performance during sustained exercise activity. In the body, citrullination is an important biochemical reaction in proteins which involves post-translational hydrolysis of arginine residues to form citrulline residues and ammonia. Proteins modified through extensive citrullination play a key role in the pathogenesis of a variety of diseases such as multiple sclerosis, autoimmune disorders, and potentially cancer. In our studies, we describe the experimental results of a structure determination using highly accurate X-ray data that were collected at low temperature (125 K). Through intensive crystallization studies, we obtained the delta polymorph of citrulline. There are seven strong N-H…O hydrogen bonds, an unusually high number for a small molecule. We utilized computational methods to understand the complex biochemistry of citrulline/arginine. Our DFT investigation offers clues for describing and understanding the complex biochemistry of citrulline/arginine. In addition, it is evident that the hydrolysis of arginine to citrulline is energetically favored and can be considered a driving force for important citrullination reactions.

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Acknowledgements

X-ray facilities were provided by the US National Science Foundation (Grant No. 0521237). We are indebted to Professor Lou Massa for transmitting his vast knowledge of quantum chemistry with enthusiasm and wit and congratulate him on his Festschrift.

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Authors and Affiliations

  1. Department of Chemistry, Vassar College, Poughkeepsie, NY, 12604, USA

    Alessio Caruso, Miriam Rossi & Francesco Caruso

  2. Department of Computing & Information Services, Vassar College, Poughkeepsie, NY, 12604, USA

    Christopher Gahn

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  1. Alessio Caruso
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  2. Miriam Rossi
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  3. Christopher Gahn
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  4. Francesco Caruso
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Correspondence to Miriam Rossi.

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The authors declare that they have no conflict of interest.

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This paper is dedicated to Professor Lou Massa on the occasion of his Festschrift: A Path through Quantum Crystallography.

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Caruso, A., Rossi, M., Gahn, C. et al. A structural and computational study of citrulline in biochemical reactions. Struct Chem 28, 1581–1589 (2017). https://doi.org/10.1007/s11224-017-0996-x

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