Tryptophan synthase: a mine for enzymologists

Abstract

Tryptophan synthase is a pyridoxal 5'-phosphate-dependent alpha(2)beta(2) 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) alpha- and beta-active sites are separated by about 20 A 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 alpha-active site, is intramolecularly channeled to the beta-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.

Indoleamine 2,3-Dioxygenase 1 Is a Lung-Specific Innate Immune Defense Mechanism That Inhibits Growth ofFrancisella tularensisTryptophan Auxotrophs

“…These two chains on May 10, 2018 by guest http://iai.asm.org/ make up the tetrameric ␣ 2 ␤ 2 tryptophan synthase enzyme complex that catalyzes the final steps in tryptophan biosynthesis. The ␣ subunits convert indole-3-glycerolphosphate to indole and glyceraldehyde 3-phosphate, while the ␤ subunits catalyze the condensation of indole and serine to tryptophan (8,25,30). The trpA and trpB genes are positioned next to each other in the Francisella genome (Fig.…”

Kynurenine pathway metabolism and the microbiota-gut-brain axis

“…Indeed, tryptophan itself can be synthesised via the shikimic acid pathway in bacteria and plants (Maeda and Dudareva, 2012;Martinez et al, 2015) with the last two steps of bacterial tryptophan biosynthesis catalysed by tryptophan synthase (Raboni et al, 2009;Yanofsky, 2007). Given that tryptophan synthesis is energetically expensive for cells and that it is usually readily available via dietary proteins (Priya et al, 2014), the evolutionary loss of this feature in mammals is understandable.…”

Influence of the tryptophan-indole-IFNγ axis on human genital Chlamydia trachomatis infection: role of vaginal co-infections

“…C. trachomatis urogenital isolates only have a subset of trp genes, encoded in the plasticity zone: trpR , encoding a trp repressor; and trpA and trpB , encoding homologs of the α (TrpA) and β (TrpB) subunits of tryptophan synthase. As reviewed recently (Raboni et al, 2009; Miles, 2013), tryptophan synthase is a tetramer consisting of two α subunits and two β subunits (α2β2). Functional and sequence analyses indicate that in most bacterial species that express a α2β2 tetramer, the enzyme is predicted to be bi-functional and catalyze the cleavage of indole glycerol-3-phosphate (IGP) to indole and glyceraldehyde-3-phosphate (TrpA catalyzed α reaction), followed by the reaction of indole with serine to form tryptophan (TrpB catalyzed β-replacement reaction) (Xie et al, 2002b; Raboni et al, 2009; Miles, 2013).…”