Disease relevance of indole-3-glycerol-P

• Two monoclonal antibodies directed against the native beta 2 subunit of Escherichia coli tryptophan synthase [L-serine hydro-lyase (adding indoleglycerol-phosphate), EC 4.2.1.20], one recognizing the C-terminal F1 domain and the other the N-terminal F2 domain, were used to detect immunoreactive intermediates in the folding of the protein [1].
• The crystal structure of indoleglycerol-phosphate synthase from Thermotoga maritima. Kinetic stabilization by salt bridges [2].
• The roles of indoleglycerol phosphate and the TrpI protein in the expression of trpBA from Pseudomonas aeruginosa [3].
• Sequence of the indoleglycerol phosphate synthase (trpC) gene from Rhodobacter capsulatus [4].
• Amino-terminal sequences of indoleglycerol phosphate synthetase of Escherichia coli and Salmonella typhimurium [5].

High impact information on indole-3-glycerol-P

• By combining an existing binding site for structural elements of phosphoribosylanthranilate with a catalytic template required for isomerase activity, we are able to evolve phosphoribosylanthranilate isomerase activity from the scaffold of indole-3-glycerol-phosphate synthase [6].
• Based on the mutant phenotypes, we propose that a particular sequence of protein--protein and protein--DNA interactions is required for activation of trpPB by TrpI and InGP [7].
• Our hypothesis holds that the trpA type of "indole-utilization" mutation alters the repressor (synthase alpha-chain) so that indole as well as indole-3-glycerol-P serves as an effector molecule for tryptophan synthase induction [8].
• We propose that the alpha-chain of the synthase has an autogenous regulatory function, serving as the repressor or the indole-3-glycerol-P recognition component of the repressor of the trpAB operon (synthase alpha-and beta-chains) [8].
• According to the kinetic parameters of the purified isomerase protein, the enzyme is more active than, for example, the purified TRP3 enzyme indoleglycerol-phosphate synthase [9].

Chemical compound and disease context of indole-3-glycerol-P

• Limited proteolysis of N-(5'-phosphoribosyl)anthranilate isomerase: indoleglycerol phosphate synthase from Escherichia coli yields two different enzymically active, functional domains [10].
• By comparison to the non-differentiating enteric bacteria in which these two enzymes are fused into a single polypeptide, the isolation of the indoleglycerol phosphate synthase and phosphoribosyl anthranilate isomerase from B. subtilis has demonstrated that the two proteins are separate species in this organism [11].
• The alpha subunit of the Escherichia coli tryptophan synthase catalyzes the reversible aldolytic reaction: Indole-3-glycerol phosphate in equilibrium indole + glyceraldehyde 3-phosphate [12].

Biological context of indole-3-glycerol-P

• In E. coli minicells, the plasmid insert directed the synthesis of polypeptides of 44,000, 33,000, and 20,000 daltons, molecular masses that are consistent with the reported molecular masses of phosphoribosylanthranilate transferase, indoleglycerol-phosphate synthase, and anthranilate-synthase component II, respectively [13].
• However, the phosphoribosyl anthranilate isomerase domain appears to stabilize the indoleglycerol phosphate synthase domain of the bifunctional enzyme from Escherichia coli by interactions that seem to subtly influence the kinetics of ligand binding [14].
• The role of the extra helix alpha zero in the N-terminal extension of the eight-fold beta alpha barrel of indoleglycerol phosphate synthase was probed by point mutation and truncation [15].
• Deletion mutagenesis as a test of evolutionary relatedness of indoleglycerol phosphate synthase with other TIM barrel enzymes [15].
• Isolation of the DNA sequence coding indole-3-glycerol phosphate synthetase and phosphoribosylanthranilate isomerase of Schizophyllum commune [16].

Associations of indole-3-glycerol-P with other chemical compounds

• Cryo-crystallography of a true substrate, indole-3-glycerol phosphate, bound to a mutant (alphaD60N) tryptophan synthase alpha2beta2 complex reveals the correct orientation of active site alphaGlu49 [17].
• A second 56,000-Da fragment, which behaved as an asymmetric dimer (apparent molecular weight 140,000) on gel filtration, retained both N-(5'-phosphoribosyl)anthranilate isomerase and indole-3-glycerol phosphate synthase activity [18].
• These data prove that the alpha and beta active sites communicate reciprocally and explain why the turnover number for the physiological reaction of indoleglycerol phosphate with L-serine greatly exceeds that of the cleavage reaction of indoleglycerol phosphate [19].
• Neither indoleglycerol-phosphate synthase nor anthranilate synthase were affected significantly in the ssb mutant [20].
• The data suggested that a farnesyl residue derived from the mevalonate pathway and an anthranilate-derived indole-3-glycerol phosphate residue are condensed, and then cyclization occurs along with rearrangement to form the indolosesquiterpene core [21].

Gene context of indole-3-glycerol-P

• It is suggested that the TRP1 gene of Saccharomyces cerevisiae might be the result of a rearrangement event, separating the N-(5'-phosphoribosyl-1)-anthranilate isomerase domain from the indoleglycerol-phosphate synthase domain and putting the catalytically more active isomerase domain behind a weak and nonregulated constitutive promoter [9].
• The results show that four of the five activities examined are stable under most nongrowing conditions, whereas one activity, indoleglycerol phosphate (InGP) synthetase, carried by the trpC protein, is unstable under most conditions tested [22].
• The Pseudomonas aeruginosa tryptophan synthase genes, trpA and trpB, which are induced by their substrate indoleglycerol phosphate, were cloned along with their controlling region into the BamHI site of pBR322 to produce the 10.7-megadalton plasmid pZAZ5 [23].
• Expression of the trpBA gene pair of Pseudomonas aeruginosa is regulated by the endogenous level of indoleglycerol phosphate (InGP) and the trpI gene product [24].
• The majority of the enzymatically defective mutant alpha subunits have decreased capacities for substrate (indole-3-glycerol phosphate) utilization, typical of the early trpA missense mutants isolated by in vivo selection methods [25].

Analytical, diagnostic and therapeutic context of indole-3-glycerol-P

• Here, we investigated the enzymatic reaction mechanism through X-ray crystallography of complexes of the hyperthermostable enzyme from Sulfolobus solfataricus with the substrate 1-(o-carboxyphenylamino) 1-deoxyribulose 5-phosphate, a substrate analogue and the product indole-3-glycerol phosphate [26].
• To obtain a better understanding of this sluggishness, we used DNA shuffling to mutagenize the trpC gene, which encodes indoleglycerol phosphate synthase, from the hyperthermophile Sulfolobus solfataricus [27].

References