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Revisiting the allosteric mechanism of aspartate transcarbamoylase

Nature Structural Biology volume 9, pages 87–88 (2002)Cite this article

In an elegant work, Macol et al.1 claim to prove that the binding energy of a single bisubstrate molecule (PALA) to one of the six active sites of Escherichia coli aspartate transcarbamoylase (ATCase) is sufficient to entirely shift the T to R quaternary structure equilibrium2 into the R state. To this aim, they designed a hybrid enzyme containing a single functional active site, with the other five sites rendered incapable of binding PALA by a point mutation. Although the authors' conclusion is reasonable for the hybrid enzyme, we believe that its extension to the wild type enzyme, the real issue at stake, is not warranted.

The numerical values derived from our simple analysis are only crude approximations. However, they clearly show that the presented data do not fully support the authors' claim. To prove the case, the authors' experimental rationale requires a mutation abolishing PALA binding to the active site without modifying the T state stability. The quantitative study of the T to R quaternary structure transition of the resulting hybrid enzyme built from such a mutant would then provide a test of the implicit assumption of their model — namely that the local conformational changes induced by substrate binding and the quaternary structure transition are linked in an all-or-none fashion, a view already challenged by a combined fluorescence and SAXS study6.

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Figure 1: Small-angle X-ray scattering.

References

  1. Macol, C.P., Tsuruta, H., Stec, B. & Kantrowitz, E.R. Nature Struct. Biol. 8, 423–426 (2001).

    Article  CAS  Google Scholar 

  2. Monod, J., Wyman, J. & Changeux, J.P. J. Mol. Biol. 12, 88–118 (1965).

    Article  CAS  Google Scholar 

  3. Svergun, D.I., Barberato, C., Koch, M.H., Fetler, L. & Vachette, P. Proteins 27, 110–117 (1997).

    Article  CAS  Google Scholar 

  4. Howlett, G.J., Blackburn, M.N., Compton, J.G. & Schachman, H.K. Biochemistry 16, 5091–5099 (1977).

    Article  CAS  Google Scholar 

  5. Fetler, L., Tauc, P., Hervé, G., Moody, M.F. & Vachette, P. J. Mol. Biol. 251, 243–255 (1995).

    Article  CAS  Google Scholar 

  6. Fetler, L., Vachette, P., Hervé, G. & Ladjimi, M.M. Biochemistry 34, 15654–15660 (1995).

    Article  CAS  Google Scholar 

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  1. LURE (CNRS, CEA, MER), Bâtiment 209D, B.P. 34, Université Paris-Sud, Orsay, 91898, Cedex, France

    Luc Fetler & Patrice Vachette

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  1. Luc Fetler
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  2. Patrice Vachette
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Correspondence to Luc Fetler or Patrice Vachette.

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Fetler, L., Vachette, P. Revisiting the allosteric mechanism of aspartate transcarbamoylase. Nat Struct Mol Biol 9, 87–88 (2002). https://doi.org/10.1038/nsb0202-87

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