Indoleglycerol 3-phosphate

Figure 4.7 Two of the enzymatic activities involved in the biosynthesis of tryptophan in E. coli, phosphoribosyl anthranilate (PRA) isomerase and indoleglycerol phosphate (IGP) synthase, are performed by two separate domains in the polypeptide chain of a bifunctional enzyme. Both these domains are a/p-barrel structures, oriented such that their active sites are on opposite sides of the molecule. The two catalytic reactions are therefore independent of each other. The diagram shows the IGP-synthase domain (residues 48-254) with dark colors and the PRA-isomerase domain with light colors. The a helices are sequentially labeled a-h in both barrel domains. Residue 255 (arrow) is the first residue of the second domain. (Adapted from J.P. Priestle et al., Proc.

This pyridoxal-phosphate-dependent enzyme [EC 4.2.1.20] catalyzes the reaction of L-serine with l-(indol-3-yl)glycerol 3-phosphate to produce L-tryptophan and glyceraldehyde 3-phosphate. The enzyme will also catalyze (a) the conversion of serine and indole into tryptophan and water and (b) conversion of indoleglycerol phosphate into indole and glyceraldehyde phosphate. 

A (3 replacement reaction catalyzed by the PLP-dependent tryptophan synthase converts indoleglycerol phosphate and serine to tryptophan. Tryptophan synthase from E. coli consists of two subunits associated as an a2P2 tetramer (Fig. 25-3). The a subunit catalyzes the cleavage (essentially a reverse aldol) of indoleglycerol phosphate to glyceraldehyde 3-phosphate and free indole (Fig. 25-2, step s).67 The P subunit contains PLP. It presumably generates, from serine, the Schiff base of aminoacrylate, as indicated in Fig. 25-2 (step f). The enzyme catalyzes the addition of the free indole to the Schiff base to form tryptophan. The indole must diffuse for a distance of 2.5 ran... 

The biosynthesis of tryptophan from the branchpoint compound, chorismate in E. coli The first step involves the conversion of chorismate to the aromatic compound anthranilate. The anthranilate is transferred to a ribose phosphate chain. The product is cyclized to indoleglycerol phosphate by the removal of water and loss of the ring carboxyl by indoleglycerol phosphate synthase. Finally, in a... 

Among different organisms the five enzyme activities required for tryptophan synthesis are distributed on different proteins (table 21.1). For example, in E. coli, indoleglycerol phosphate synthase catalyzes both the isomerization of phosphoribosylanthranilate and the cyclization step. Of particular interest is the occurrence of a single protein of the catalytic activities for nonconsecutive reactions in some cases. If in such cases the proteins were separate from each other in the cell, this arrangement, for example, in Neurospora, would necessitate the product of one reaction leaving the product site of one enzyme to be acted on by another... 

Fig. 1. The tryptophan biosynthetic pathway. Abbreviations AS, anthranilate synthetase PRPP, 5-phosphoribosyI-l-pyrophosphate PRT, phosphoribosyi transferase PRAI, phosphoribosyi anthranilate isomerase InGPS, indoleglycerol phosphate synthetase TS, tryptophan synthetase TS-a, tryptophan synthetase a-chain subunit TS- z, tryptophan synthetase -chain dimer subunit.

Fig. 4. Diagram of the tryptophan operon plus two neighboring genes. The gene designations for both E. coli and S. typhimurium are given. The supX locus has not been identified in E. coli. Controlling elements PI, the promoter associated with the operator 0, the operator P2, the low-efficiency internal promoter. Enzymes AS-I, anthianilate synthetase component I PRT, phosphoribosyl transferase (AS-II, anthianilate synthetase component II) PRAI, phosphoribosyl anthianilate isomerase InGPS, indoleglycerol phosphate synthetase TS-a, tryptophan synthetase a-chain TS-)S, tryptophan synthetase j8-chain. RUM, region of unusual mutations in S. typhimurium.

The L-tryptophan synthetases of fungal origin which have been studied appear to be quite different from the bacterial enzyme. A single undissociable protein species catalyses the biosynthetic reaction from indoleglycerol phosphate (38) to L-tryptophan (3) and the reactions (z) and and a mutant of Newospora... 

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