Tryptophan synthase: a mine for enzymologists

• Published in: Cellular and molecular life sciences : CMLS Vol. 66; no. 14; pp. 2391 - 2403
• Main Authors: Raboni, Samanta, Bettati, Stefano, Mozzarelli, Andrea
• Format: Journal Article
• Language: English
• Published: Basel Basel : SP Birkhäuser Verlag Basel 01-07-2009; SP Birkhäuser Verlag Basel; Springer Nature B.V
• Subjects: Allosteric properties; Allosteric Regulation; Amino acids; Binding Sites; Biocatalysis; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biosynthesis; Cell Biology; Cellular biology; Enzymes; Indoles - chemistry; Kinetics; Life Sciences; Ligands; Models, Chemical; Models, Molecular; Protein Binding; Protein Conformation; Protein Structure, Secondary; Protein Structure, Tertiary; Pyridoxal Phosphate - metabolism; Review; Studies; Tryptophan Synthase - chemistry; Tryptophan Synthase - metabolism; X-ray crystallography; Tryptophan; Pyridoxal 5′-phosphate; Enzyme catalysis; Conformational changes
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-009-0028-0

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.