To understand the mechanisms of tryptophan synthase, the structure of the enzyme must first be studied. The general form of the enzyme is an α2β2 complex in which the α subunit forms a TIM barrel and the β subunit has a type II fold conformation.[1] Additionally, the enzyme has two binding sites: an indole 3-glycerol binding site and an indole and serine binding site. Another important feature that allows for the tryptophan synthase to perform its function is its hydrophobic channel which makes it possible for indoles to diffuse to the appropriate site instead of diffusing out to cell’s cytosol.[2]
Function
The mechanism of tryptophan synthase can be described in two steps. These steps are the last two in the synthesis of tryptophan. They include the loss of glyceraldehyde 3-phosphate from indole 3-glyserinphosphate forming indole and then the change from indole into tryptophan via the binding of serine and loss of water.
Relevance
The production of tryptophan takes place not in animals but in all other kingdoms such as plants, fungi, and bacteria because the enzyme is only present in these organisms. If humans could somehow inhibit this enzyme in those organisms, it would be an effective way to treat certain diseases without having harmful effects on humans. Such diseases as tuberculosis, ocular and genital infections, and cryptosporidiosis could be potential targets and, herbicides could be made using chemicals which inhibit this enzyme in plants as well.
Structural highlights
The structure of Tryptophan Synthase is in an alpha-beta-beta-alpha complex with two binding sites: an indole 3-glycerol binding site and an indole and serine binding site.In Salmonella typhimurium, studies have shown the relevance of its monovalent cation site (MVC), which is necessary for catalysis and regulation of substrate channeling [3]. This site is also directly related to the reaction between the α2β2 complex of tryptophan synthase and the L-serine by regulating the distribution of intermediates within this reaction.It activates Tryptophan synthase by binding to its allosteric site which is positioned near the PLP cofactor of the enzyme [4]. Examples of these cations bounded by the enzyme in vitro include Sodium, Potassium, Cesium, Lithium, Rubidium, Ammonium, and Guanidinium ions.
Without the MVC to bind these cations, the enzyme can not be converted to the stabilized α-aminoacrylate species E(A-A).The E(A-A) that is not activated will have a closed #946;-subunit conformationDierkers, Adam T., et al. "Tryptophan synthase: structure and function of the monovalent cation site." Biochemistry 48.46 (2009): 10997-11010. This means that the indole with not be able accepted through the tunnel that is described below.
The structure of the this tunnel between the active site and indole binding site in can be seen by clicking this link: (both scenes taken from the Swiss Protein Database Viewer code 3CEP), and the full structure from which this was taken can be seen by clicking the highlighted "Tryptophan Synthase" in the previous sentence. When the MVC binds the Sodium ion, it is able to receive the indole that is then bound to serine in order to create the final product: tryptophan.
