Tryptophan synthase

Tryptophan synthase or tryptophan synthetase is an enzyme that catalyzes the final two steps in the biosynthesis of tryptophan. It is commonly found in Eubacteria, Archaebacteria, Protista, Fungi, and Plantae. However, it is absent from Animalia. It is typically found as an α2β2 tetramer. The α subunits catalyze the reversible formation of indole and glyceraldehyde-3-phosphate (G3P) from indole-3-glycerol phosphate (IGP). The β subunits catalyze the irreversible condensation of indole and serine to form tryptophan in a pyridoxal phosphate (PLP) dependent reaction. Each α active site is connected to a β active site by a 25 angstrom long hydrophobic channel contained within the enzyme. This facilitates the diffusion of indole formed at α active sites directly to β active sites in a process known as substrate channeling. The active sites of tryptophan synthase are allosterically coupled. Tryptophan synthase or tryptophan synthetase is an enzyme that catalyzes the final two steps in the biosynthesis of tryptophan. It is commonly found in Eubacteria, Archaebacteria, Protista, Fungi, and Plantae. However, it is absent from Animalia. It is typically found as an α2β2 tetramer. The α subunits catalyze the reversible formation of indole and glyceraldehyde-3-phosphate (G3P) from indole-3-glycerol phosphate (IGP). The β subunits catalyze the irreversible condensation of indole and serine to form tryptophan in a pyridoxal phosphate (PLP) dependent reaction. Each α active site is connected to a β active site by a 25 angstrom long hydrophobic channel contained within the enzyme. This facilitates the diffusion of indole formed at α active sites directly to β active sites in a process known as substrate channeling. The active sites of tryptophan synthase are allosterically coupled. Subunits: Tryptophan synthase typically exists as an α-ββ-α complex. The α and β subunits have molecular masses of 27 and 43 kDa respectively. The α subunit has a TIM barrel conformation. The β subunit has a fold type II conformation and a binding site adjacent to the active site for monovalent cations. Their assembly into a complex leads to structural changes in both subunits resulting in reciprocal activation. There are two main mechanisms for intersubunit communication. First, the COMM domain of the β-subunit and the α-loop2 of the α-subunit interact. Additionally, there are interactions between the αGly181 and βSer178 residues. The active sites are regulated allosterically and undergo transitions between open, inactive, and closed, active, states. Indole-3-glycerol binding site: See image 1. Indole and serine binding site: See image 1. Hydrophobic channel: The α and β active sites are separated by a 25 angstrom long hydrophobic channel contained within the enzyme allowing for the diffusion of indole. If the channel did not exist, the indole formed at an α active site would quickly diffuse away and be lost to the cell as it is hydrophobic and can easily cross membranes. As such, the channel is essential for enzyme complex function. α subunit reaction: The α subunit catalyzes the formation of indole and G3P from a retro-aldol cleavage of IGP. The αGlu49 and αAsp60 are thought to be directly involved in the catalysis as shown. The rate limiting step is the isomerization of IGP. See image 2. β subunit reaction: The β subunit catalyzes the β-replacement reaction in which indole and serine condense to form tryptophan in a PLP dependent reaction. The βLys87, βGlu109, and βSer377 are thought to be directly involved in the catalysis as shown. Again, the exact mechanism has not been conclusively determined. See image 2. Net reaction: See image 3. Tryptophan synthase is commonly found in Eubacteria, Archaebacteria, Protista, Fungi, and Plantae. It is absent from animals such as humans. Tryptophan is one of the twenty standard amino acids and one of nine essential amino acids for humans. As such, tryptophan is a necessary component of the human diet.