Cellular and Molecular Life Sciences

, Volume 66, Issue 14, pp 2391–2403 | Cite as

Tryptophan synthase: a mine for enzymologists

  • Samanta Raboni
  • Stefano Bettati
  • Andrea MozzarelliEmail author


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.


Enzyme catalysis Pyridoxal 5′-phosphate Conformational changes Tryptophan X-ray crystallography 



Glycerol phosphate






Indoleacetyl aspartate


Indoleacetyl glycine


Indoleacetyl valine


Indole-3-glycerol phosphate


Indole 3-propanol phosphate


Pyridoxal 5′-phosphate


Tryptophan synthase



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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Copyright information

© Birkhäuser Verlag, Basel/Switzerland 2009

Authors and Affiliations

  • Samanta Raboni
    • 1
    • 3
  • Stefano Bettati
    • 1
    • 2
  • Andrea Mozzarelli
    • 1
    • 2
    Email author
  1. 1.Department of Biochemistry and Molecular BiologyUniversity of ParmaParmaItaly
  2. 2.Italian National Institute of Biostructures and BiosystemsParmaItaly
  3. 3.CRIBI Biotechnology Centre, University of PaduaPaduaItaly

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