Tryptophan synthase, an allosteric molecular factory

• Published in: Current opinion in chemical biology Vol. 12; no. 5; pp. 593 - 600
• Main Authors: Barends, Thomas RM, Dunn, Michael F, Schlichting, Ilme
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-10-2008
• Subjects: Allosteric Regulation; Biocatalysis; Biomimetic Materials - chemistry; Biomimetic Materials - metabolism; Protein Multimerization; Salmonella typhimurium; Substrate Specificity; Tryptophan Synthase - chemistry; Tryptophan Synthase - metabolism
• ISSN: 1367-5931; 1879-0402
• DOI: 10.1016/j.cbpa.2008.07.011

Tryptophan synthase (TrpS) is a pyridoxal phosphate-containing bifunctional enzyme that catalyzes the last two steps in the biosynthesis of
l-tryptophan. Indole, an intermediate generated at the active site of the α-subunit is channeled via a 25
Å long tunnel to the β-active site where it reacts with an aminoacrylate intermediate derived from
l-serine. The two reactions are kept in phase by allosteric interactions between the two subunits. The recent development of novel α-site ligands and α-reaction transition state analogs combined with kinetic and crystal structure analysis of
Salmonella typhimurium tryptophan synthase has provided new insights into the allosteric regulation of substrate channeling, the reaction mechanisms of the α and β active sites, and the influence of structural dynamics.