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An aminotransferase branch point connects purine catabolism to amino acid recycling

Nature Chemical Biology volume 6, pages 801–806 (2010)Cite this article

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Abstract

Although amino acids are known precursors of purines, a pathway for the direct recycling of amino acids from purines has never been described at the molecular level. We provide NMR and crystallographic evidence that the PucG protein from Bacillus subtilis catalyzes the transamination between an unstable intermediate ((S)-ureidoglycine) and the end product of purine catabolism (glyoxylate) to yield oxalurate and glycine. This activity enables soil and gut bacteria to use the animal purine waste as a source of carbon and nitrogen. The reaction catalyzed by (S)-ureidoglycine–glyoxylate aminotransferase (UGXT) illustrates a transamination sequence in which the same substrate provides both the amino group donor and, via its spontaneous decay, the amino group acceptor. Structural comparison and mutational analysis suggest a molecular rationale for the functional divergence between UGXT and peroxisomal alanine-glyoxylate aminotransferase, a fundamental enzyme for glyoxylate detoxification in humans.

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Figure 1: Identification of pucG as UGXT.
Figure 2: Aminotransferase activity of UGXT.
Figure 3: UGXT structure.
Figure 4: Evolution of substrate specificity in UGXT proteins.

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Acknowledgements

We thank L. Borghi, A. Nouvenne and F. Albertini for discussions, and the staff of beamline XRD1 of Elettra, Trieste, for technical assistance during data collection.

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Author notes

  1. Roberto Costa

    Present address: Present address: Department of Biological Chemistry, University of Padua, Padua, Italy.,

  2. Ileana Ramazzina and Roberto Costa: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, University of Parma, Parma, Italy

    Ileana Ramazzina, Roberto Costa, Rodolfo Berni, Alessio Peracchi & Riccardo Percudani

  2. Department of Biological Chemistry, University of Padua, Padua, Italy

    Laura Cendron & Giuseppe Zanotti

  3. Venetian Institute of Molecular Medicine, Padua, Italy

    Laura Cendron & Giuseppe Zanotti

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  1. Ileana Ramazzina
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Contributions

I.R. and R.C. performed experiments. L.C., R.B. and G.Z. performed the crystallographic studies. R.P. and A.P. designed experiments. R.P. conceived the study and wrote the paper with contributions from A.P. and G.Z. All authors analyzed data, discussed results and approved the final manuscript.

Corresponding author

Correspondence to Riccardo Percudani.

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The authors declare no competing financial interests.

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Supplementary Methods, Supplementary Tables 1–3 and Supplementary Figures 1–8 (PDF 1336 kb)

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Ramazzina, I., Costa, R., Cendron, L. et al. An aminotransferase branch point connects purine catabolism to amino acid recycling. Nat Chem Biol 6, 801–806 (2010). https://doi.org/10.1038/nchembio.445

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