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Tryptophan synthase: a mine for enzymologists

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Abstract

Tryptophan synthase is a pyridoxal 5′-phosphate-dependent α2β2 complex catalyzing the last two steps of tryptophan biosynthesis in bacteria, plants and fungi. Structural, dynamic and functional studies, carried out over more than 40 years, have unveiled that: (1) α- and β-active sites are separated by about 20 Å and communicate via the selective stabilization of distinct conformational states, triggered by the chemical nature of individual catalytic intermediates and by allosteric ligands; (2) indole, formed at α-active site, is intramolecularly channeled to the β-active site; and (3) naturally occurring as well as genetically generated mutants have allowed to pinpoint functional and regulatory roles for several individual amino acids. These key features have made tryptophan synthase a text-book case for the understanding of the interplay between chemistry and conformational energy landscapes.

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Fig. 1
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Fig. 3

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Abbreviations

GP:

Glycerol phosphate

G3P:

d-glyceraldehyde-3-phosphate

IA:

trans-3-indole-3′-acrylate

IAD:

Indoleacetyl aspartate

IAG:

Indoleacetyl glycine

IAV:

Indoleacetyl valine

IGP:

Indole-3-glycerol phosphate

IPP:

Indole 3-propanol phosphate

PLP:

Pyridoxal 5′-phosphate

TS:

Tryptophan synthase

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Acknowledgments

We gratefully thank Dr. Francesca Spyrakis for help in the preparation of Figs. 1 and 2. This work was supported by a grant from the Italian Ministry of University and Research (COFIN2007 to A.M.).

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  1. Samanta Raboni

    Present address: CRIBI Biotechnology Centre, University of Padua, Padua, Italy

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, University of Parma, Viale GP Usberti 23/A, 43100, Parma, Italy

    Samanta Raboni, Stefano Bettati & Andrea Mozzarelli

  2. Italian National Institute of Biostructures and Biosystems, Parma, Italy

    Stefano Bettati & Andrea Mozzarelli

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  1. Samanta Raboni
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Correspondence to Andrea Mozzarelli.

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Raboni, S., Bettati, S. & Mozzarelli, A. Tryptophan synthase: a mine for enzymologists. Cell. Mol. Life Sci. 66, 2391–2403 (2009). https://doi.org/10.1007/s00018-009-0028-0

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