Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ANTHRANILIC ACID”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,243 records · Page 69Linked to original sources
PubMed1981

Derivation of Aromatic Amino Acid Mutants from a Methanol-Utilizing Yeast, Hansenula polymorpha.

Three classes of mutants, deregulated to enhance the flow of aromatic intermediates through the tryptophan biosynthetic branch, were obtained. 5-Fluorotryptophan, an antimetabolite of tryptophan, was employed to obtain one class of deregulated mutants. By sequential resistance development, three resistant mutants were isolated. Hansenula polymorpha strains showed greater sensitivity to 5-fluorotryptophan when growing on methanol than when growing on glucose. Yeast extract stimulated the production of total indole metabolites (indoles) by wild-type and mutant strains, with each 5-fluorotryptophan mutant producing higher amounts of these metabolites than its predecessor. Two other mutant classes were isolated: (i) a mutant resistant to anthranilate (an inhibitory intermediate in the tryptophan biosynthetic branch) and (ii) a phenylalanine-plus-tyrosine bradytroph. Each of these produced a higher extracellular titer of total indoles than its immediate parent. With respect to the overproduction of indoles, resistance to 5-fluorotryptophan was a more useful selection method than were anthranilate resistance and phenylalanine-plus-tyrosine bradytrophy.

Journal Article↗
PubMed2006

Metabolic changes in Arabidopsis thaliana expressing the feedback-resistant anthranilate synthase alpha subunit gene OASA1D.

Anthranilate synthase (AS) is a key enzyme in tryptophan (Trp) biosynthesis. Metabolic changes in transgenic Arabidopsis plants expressing the feedback-resistant anthranilate synthase alpha subunit gene OASA1D were investigated with respect to Trp synthesis and effects on secondary metabolism. The Trp content varied depending on the transgenic line, with some lines showing an approximately 200-fold increase. The levels of AS activity in crude extracts from the transgenic lines were comparable to those in the wild type. On the other hand, the enzyme prepared from the lines accumulating high levels of Trp showed a relaxed feedback sensitivity. The AS activity, determined in the presence of 50 microM L-Trp, correlated well with the amount of free Trp in the transgenic lines, indicating the important role of feedback inhibition in control of Trp pool size. In Arabidopsis, Trp is a precursor of multiple secondary metabolites, including indole glucosinolates and camalexin. The amount of indol-3-ylmethyl glucosinolate (I3 M) in rosette leaves of the high-Trp accumulating lines was 1.5- to 2.1-fold greater than that in wild type. The treatment of the leaves with jasmonic acid resulted in a more pronounced accumulation of I3 M in the high-Trp accumulating lines than in wild type. The induction of camalexin formation after the inoculation of Alternaria brassicicola was not affected by the accumulation of a large amount of Trp. The accumulation of constitutive phenylpropanoids and flavonoids was suppressed in high-Trp accumulating lines, while the amounts of Phe and Tyr increased, thereby indicating an interaction between the Trp branch and the Phe and Tyr branch in the shikimate pathway.

Anthranilate Synthase↗
PubMed1989

Interpathway regulation of the TRP4 gene of yeast.

Two regulatory proteins, PHO2 and the general control regulator GCN4, bind in vitro to the promoter of the tryptophan biosynthetic TRP4 gene; the TRP4 gene product catalyses the phosphoribosylation of anthranilate. PHO2 binds specifically to the TRP4 promoter, but does not bind to any other TRP promoter. PHO2 and GCN4 proteins bind in a mutually exclusive manner to the same sequence, UAS1, one of two GCN4 binding sites in the TRP4 promoter. UAS1 is the major site for GCN4-dependent TRP4 activation. The second GCN4 binding site, UAS2, interacts with GCN4 alone. PHO2 binding interferes with the general control response of TRP4 under low phosphate conditions and simultaneous amino acid starvation and thus the PHO2 regulatory protein connects phosphate metabolism and amino acid biosynthesis in yeast. The GCN4 protein mediates the response of the transcriptional apparatus to the environmental signal 'amino acid limitation', while PHO2 seems to be the phosphate sensor that adjusts the response to the availability of phosphate precursors.

Base Sequence↗
PubMed2006

Identification and optimization of anthranilic sulfonamides as novel, selective cholecystokinin-2 receptor antagonists.

A high throughput screening approach to the identification of selective cholecystokinin-2 receptor (CCK-2R) ligands resulted in the discovery of a novel series of antagonists, represented by 1-[2-[(2,1,3-benzothiadiazol-4-ylsulfonyl)amino]-5-chlorobenzoyl]-piperidine (1; CCK-2R, pK(I) = 6.4). Preliminary exploration of the structure-activity relationships around the anthranilic ring and the amide and sulfonamide moieties led to a nearly 50-fold improvement of receptor affinity and showed a greater than 1000-fold selectivity over the related cholecystokinin-1 receptor. Pharmacokinetic evaluation led to the identification of 4-[4-iodo-2-[(5-quinoxalinylsulfonyl)amino]benzoyl]-morpholine, 26d, a compound that demonstrates promising pharmacokinetic properties in the rat and dog with respect to plasma clearance and oral bioavailability and is a potent inhibitor in vivo of pentagastrin-stimulated acid secretion in the rat when dosed orally.

Animals↗
PubMed1977

[Pharmacology and toxicology of etofenamate. 1st Communication (author's transl)].

1. The reliable antiphlogistic action of 2-(2-hydroxyethoxy)-ethyl-N-(a,a,a-trifluoro-m-tolyl)-anthranilate (etofenamate active principle of Rheumon Gel) in various experimental inflammatory models in animals is demonstrated following oral and cutaneous administration. 2. The proven inhibition of inflammatory edema by chronic administration of Rheumon gel evidences the percutaneous absorption of the active principle through the intact skin. 3. The effect of Rheumon gel sets in independently of whether the gel is applied to normal or to pathologically inflamed tissue areas. 4. Gastrointestinal mucous tolerance is better for etofenamate than for flufenamic acid, phenylbutazone and other anti-inflammatory drugs.

Animals↗
PubMed2003

Histidine ligand protonation and redox potential in the rieske dioxygenases: role of a conserved aspartate in anthranilate 1,2-dioxygenase.

The Rieske dioxygenase, anthranilate 1,2-dioxygenase, catalyzes the 1,2-dihydroxylation of anthranilate (2-aminobenzoate). As in all characterized Rieske dioxygenases, the catalytic conversion to the diol occurs within the dioxygenase component, AntAB, at a mononuclear iron site which accepts electrons from a proximal Rieske [2Fe-2S] center. In the related naphthalene dioxygenase (NDO), a conserved aspartate residue lies between the mononuclear and Rieske iron centers, and is hydrogen-bonded to a histidine ligand of the Rieske center. Engineered substitutions of this aspartate residue led to complete inactivation, which was proposed to arise from elimination of a productive intersite electron transfer pathway [Parales, R. E., Parales, J. V., and Gibson, D. T. (1999) J. Bacteriol. 181, 1831-1837]. Substitutions of the corresponding aspartate, D218, in AntAB with alanine, asparagine, or glutamate also resulted in enzymes that were completely inactive over a wide pH range despite retention of the hexameric quaternary structure and iron center occupancy. The Rieske center reduction potential of this variant was measured to be approximately 100 mV more negative than that for the wild-type enzyme at neutral pH. The wild-type AntAB became completely inactive at pH 9 and exhibited an altered Rieske center absorption spectrum which resembled that of the D218 variants at neutral pH. These results support a role for this aspartate in maintaining the protonated state and reduction potential of the Rieske center. Both the wild-type and D218A variant AntABs exhibited substrate-dependent rapid phases of Rieske center oxidations in stopped-flow time courses. This observation does not support a role for this aspartate in a facile intersite electron transfer pathway or in productive substrate gating of the Rieske center reduction potential. However, since the single turnovers resulted in anthranilate dihydroxylation by the wild-type enzyme but not by the D218A variant, this aspartate must also play a crucial role in substrate dihydroxylation at or near the mononuclear iron site.

Acinetobacter↗
PubMed1995

Selection and Characterization of [alpha]-Methyltryptophan-Resistant Lines of Lemna gibba Showing a Rapid Rate of Indole-3-Acetic Acid Turnover.

Turnover rate is an important aspect of the regulation of plant processes by plant growth substances. To study turnover of indole-3-acetic acid (IAA), two [alpha]-methyltryptophan-resistant lines (MTR1 and MTR2) of Lemna gibba were generated by nitrosomethyl urea treatment of an inbred line derived from L. gibba G-3. In this report we describe: (a) the development of a selection system using this near isogenic line of L. gibba; (b) techniques for chemical mutation of the lines and selection for [alpha]-methyltryptophan resistance; and (c) the partial characterization of the selected lines. MTR lines contained 3-fold higher levels of anthranilate synthase activity. The enzyme in the MTR lines required higher levels of tryptophan for feedback inhibition. MTR lines also contained 8-fold higher levels of tryptophan, 3-fold higher levels of free IAA, and similar levels of total IAA compared to the inbred line. Turnover rates in the inbred and selected lines were calculated, using the first-order rate equation, based on the decrease over time in isotopic enrichment of I3C6-IAA introduced into L. gibba during a 1-h pulse period. Isotope enrichment in IAA was determined by using gas chromatography-mass spectrometry. Both MTR lines had an approximately 10-fold higher rate of IAA turnover than the parent inbred line.

Journal Article↗
PubMed1986

Purification and properties of 4-aminobenzoate hydroxylase, a new monooxygenase from Agaricus bisporus.

A new FAD-dependent monooxygenase, 4-aminobenzoate hydroxylase that catalyzes the decarboxylative hydroxylation of 4-aminobenzoate and forms 4-hydroxyaniline in the presence of NAD(P)H and O2 has been purified to homogeneity by ammonium sulfate fractionation, affinity chromatography, chromatofocusing, and Sephadex G-100 chromatography from Agaricus bisporus, a common edible mushroom. The molecular weight of the enzyme, which consists of a single polypeptide, is 49,000. The enzyme contains 0.91 mol of FAD/mol of enzyme. Stoichiometric studies show that 1 mol of 4-aminobenzoate is converted to an equimolecular amount of 4-hydroxyaniline and CO2 with the consumption of 1 mol each of NADH and molecular oxygen. Results obtained isotopically with 18O2 show that one atom of molecular oxygen is incorporated into 4-hydroxyaniline formed from 4-aminobenzoate. The enzyme is most active between pH 6.5 and 8.0 in the oxidation of NADH and between pH 6.0 and 7.5 in the case of NADPH. The Km values for 4-aminobenzoate, NADH, and O2 are 20.4, 13.6, and 200 microM, respectively, and that for NADPH is 133 microM. Other substituted benzoates with free amino and carboxyl groups in the ortho or para position (e.g. 4-aminosalicylate and anthranilate) serve as substrates for hydroxylation, but, in these cases, H2O2 is formed simultaneously with the hydroxylation. The enzyme is insensitive to the chelators of iron and copper, sodium arsenite, and KCN. Heavy metal ions and p-chloromercuribenzoate severely inhibit the enzyme enzyme

4-Aminobenzoic Acid↗
PubMed1971

Genetics of the mandelate pathway in Pseudomonas aeruginosa.

The linkage of genes governing synthesis of enzymes functional in the conversion of l(+)-mandelate to benzoate in Pseudomonas aeruginosa was studied. These genes were found to be linked in a fashion consistent with regulatory mechanisms known to govern synthesis of this inducible pathway. Surprisingly, linkage was also observed between the mandelate genes and those governing the synthesis of functionally related enzymes that participate in the catabolism of anthranilate and benzoate. These latter genes are grouped in at least three regulatory units. Some theoretical explanations for high intensity of linkage among functionally related genes whose expression is not induced by a common metabolite are discussed.

Benzoates↗
PubMed1973

Rapid regulation of an anthranilate synthase aggregate by hysteresis.

The anthranilate synthase aggregate from Bacillus subtilis is composed of two nonidentical subunits, denoted E and X, which are readily associated or dissociated. A complex of subunit E and X can utilize glutamine or ammonia as substrates in the formation of anthranilate. Partially purified subunit E is capable of using only ammonia as the amide donor in the anthranilate synthase reaction. The stability of the EX complex is strongly influenced by glutamine and by the concentrations of the subunits. Glutamine stabilizes the aggregate as a molecular species in which the velocity of the glutamine-reactive anthranilate synthase is a linear function of protein concentration. In the absence of glutamine the aggregate is readily dissociated following dilution of the extract; that is, velocity concaves upward as a function of increasing protein concentration. Reassociation of the EX complex is characterized by a velocity lag (or hysteretic response) before steady-state velocity for the glutamine-reactive anthranilate synthase is reached. We propose that association and dissociation of the anthranilate synthase aggregate may be physiologically significant and provide a control mechanism whereby repression or derepression causes disproportionate losses or gains in activity by virtue of protein-protein interactions between subunits E and X.

Ammonia↗
PubMed1972

Anthranilate synthase-anthranilate 5-phosphoribosyl 1-pyrophosphate phosphoribosyltransferase from Aerobacter aerogenes.

1. Anthranilate synthase and phosphoribosyltransferase from Aerobacter aerogenes purify simultaneously and sediment together on sucrose gradients, showing that they occur as an enzyme aggregate. Both activities of the intact aggregate are subject to inhibition by tryptophan. 2. By using appropriate auxotrophic mutants it was shown that an intact active enzyme aggregate is formed when the components come from separate mutant strains. An intact active aggregate can also be formed when one component is from Escherichia coli and the other from A. aerogenes. 3. Phosphoribosyltransferase of A. aerogenes is active when not in an aggregate with anthranilate synthase, but is not subject to tryptophan inhibition, indicating that the inhibitor site is on the anthranilate synthase component. 4. Anthranilate synthase can be active and sensitive to tryptophan inhibition when complexed with an inactive phosphoribosyltransferase. 5. Kinetic studies on the anthranilate synthase activity show that tryptophan is a competitive inhibitor with respect to chorismate and a non-competitive inhibitor with respect to either glutamine or NH(4) (+) ions. This is consistent with a sequential mechanism of the ordered type in which chorismate is the first reactant.

Binding Sites↗
PubMed1996

Localization of the vinblastine-binding site on beta-tubulin.

A fluorescent vinblastine derivative, vinblastine-4'-anthranilate, has been shown to inhibit polymerization of rat brain tubulin (IC50 = 4.8 microM). Binding of the drug to tubulin increases fluorescence intensity, causes a small emission blue shift, and has a quantum yield of 0.037. Fluorescence increases as a function of drug concentration, with a high affinity site and an undetermined number of lower affinity sites. Photolabeling, by exciting the fluorescent drug-tubulin complex at the absorption maximum of anthranilate, yields a covalent adduct confined to beta-tubulin. Its formation is specific in that it is blocked by maytansine or vinblastine. Tryptic hydrolysis identifies a single fluorescent beta-peptide coinciding with residues 175-213. The interactions between various ligands at this central portion of beta-tubulin are discussed.

Amino Acid Sequence↗
PubMed2005

Stabilization due to dimer formation of phosphoribosyl anthranilate isomerase from Thermus thermophilus HB8: X-ray Analysis and DSC experiments.

The crystal structure of phosphoribosyl anthranilate isomerase (PRAI) from Thermus thermophilus HB8 (TtPRAI) was solved at 2.0 A resolution. The overall structure of TtPRAI with a dimeric structure was quite similar to that of PRAI from Thermotoga maritima (TmPRAI). In order to elucidate the stabilization mechanism of TtPRAI, its physicochemical properties were examined using DSC, CD, and analytical centrifugation at various pHs in relation to the association-dissociation of the subunits. Based on the experimental results for TtPRAI and the structural information on TtPRAI and TmPRAI, we found that: (i) the denaturation of TtPRAI at acidic pH is correlated with the dissociation of its dimeric form; (ii) the hydrophobic interaction of TtPRAI in the monomer structure is slightly greater than that of TmPRAI, but dimer interface of the TmPRAI is remarkably greater; (iii) the contributions of hydrogen bonds and ion bonds to the stability are similar to each other; and (iv) destabilization due to the presence of cavities in TtPRAI is greater than that of TmPRAI in both the monomer and dimer structures.

Aldose-Ketose Isomerases↗
PubMed1993

Characterization of human autoantibodies reactive to gastric parietal cells.

Human sera from autoimmune gastritis patients containing autoantibodies to gastric parietal cells were analyzed by immunological methods. Enzyme linked immuno-sorbent assay demonstrated that all nine sera reacted with pig gastric vesicles enriched in H+/K(+)-ATPase (gastric proton pump). Immunoblotting experiments indicated that the alpha subunit of the H+/K(+)-ATPase was the major antigen in the vesicles with two of the sera reacting strongly. We further characterized the specificity of the antibodies using partial sequences of the pig alpha subunit fused with truncated TrpE (anthranilate synthase). The antibodies from autoimmune gastritis patients reacted differently to the two fusion proteins (Met-1 to Ala-79, and Arg-606 to Ile-964), indicating that each patient sera contains a mixture of autoantibodies recognizing different epitopes with variable contents.

Amino Acid Sequence↗
PubMed1978

Context effects on nonsense codon suppression in Escherichia coli.

The influence of mRNA context on nonsense codon suppression has been studied by suppression measurements at one site in the Escherichia coli trpE gene and at two sites in the trpA gene. The ratio of suppression efficiencies of amber and ochre codons at each site (homotopic pairs) has been compared using ochre suppressing derivatives of tRNATyr. This ratio is independent of differential effects of the inserted amino acid on enzyme function. We have found that mRNA context can change the ratio of suppression efficiencies of homotopic nonsense codons at the three sites in the trp gene system over a ten-fold range. The causes of such variation, and, in particular the effect of certain adjacent nucleotides on nonsense codon suppression are considered.

Anthranilate Synthase↗
PubMed1968

Tryptophan synthetic pathway and its regulation in Chromobacterium violaceum.

Extracts of Chromobacterium violaceum catalyzed all of the reactions involved in synthesizing tryptophan from chorismic acid. Tryptophan auxotrophs which had lost any of these activities did not produce the characteristic purple pigment, violacein, when grown on a medium in which tryptophan was limiting. Gel filtration of extracts allowed us to estimate molecular weights for the tryptophan enzymes. All of the enzymes appeared to have molecular weights below 100,000. No enzymes were observed to occur in aggregates. The specific activities of the enzymes of the tryptophan pathway did not change when mutants were grown under conditions of limiting or excess tryptophan. The first enzyme in the pathway, anthranilate synthetase, was subject to feedback control by the end product, tryptophan. Tryptophan acted as a noncompetitive inhibitor with respect to glutamine, one of the substrates for anthranilate synthetase, and as a competitive inhibitor of the reaction when chorismate, the other substrate, was varied. The nonlinearity observed in the Lineweaver-Burk plot in the latter case suggests that there may be more than one chorismate-binding site on anthranilate synthetase.

Cell-Free System↗
PubMed2006

Astrocytic energy metabolism consolidates memory in young chicks.

In a single trial discrimination avoidance learning task, chicks learn to distinguish between beads of two colors, which are dipped in either a strong or weak tasting aversant (methyl anthranilate) to induce strongly-reinforced and weakly-reinforced learning, respectively. Consolidation of strongly-reinforced learning can be prevented by inhibitors of glycolysis, such as 2-deoxyglucose and iodoacetate and by inhibitors of oxidative metabolism and the consolidation of weakly-reinforced learning can be promoted by administration of glucose. In the present study we show that bilateral, intracerebral injection of 30 nmol acetate can act like glucose to consolidate labile memory and to restore memory impaired by 2-deoxyglucose administration. Acetate is a metabolic substrate that feeds into the tricarboxylic acid cycle, it is oxidized in astrocytes, but not in neurones. Our data suggest that effects of glucose administered 15-25 min post-training on memory consolidation are mediated via astrocytes not neurons.

Acetates↗
PubMed2004

Identification and functional analysis of two aromatic-ring-hydroxylating dioxygenases from a sphingomonas strain that degrades various polycyclic aromatic hydrocarbons.

In this study, the enzymes involved in polycyclic aromatic hydrocarbon (PAH) degradation in the chrysene-degrading organism Sphingomonas sp. strain CHY-1 were investigated. [14C]chrysene mineralization experiments showed that PAH-grown bacteria produced high levels of chrysene-catabolic activity. One PAH-induced protein displayed similarity with a ring-hydroxylating dioxygenase beta subunit, and a second PAH-induced protein displayed similarity with an extradiol dioxygenase. The genes encoding these proteins were cloned, and sequence analysis revealed two distinct loci containing clustered catabolic genes with strong similarities to corresponding genes found in Novosphingobium aromaticivorans F199. In the first locus, two genes potentially encoding a terminal dioxygenase component, designated PhnI, were followed by a gene coding for an aryl alcohol dehydrogenase (phnB). The second locus contained five genes encoding an extradiol dioxygenase (phnC), a ferredoxin (phnA3), another oxygenase component (PhnII), and an isomerase (phnD). PhnI was found to be capable of converting several PAHs, including chrysene, to the corresponding dihydrodiols. The activity of PhnI was greatly enhanced upon coexpression of genes encoding a ferredoxin (phnA3) and a reductase (phnA4). Disruption of the phnA1a gene encoding the PhnI alpha subunit resulted in a mutant strain that had lost the ability to grow on PAHs. The recombinant PhnII enzyme overproduced in Escherichia coli functioned as a salicylate 1-hydroxylase. PhnII also used methylsalicylates and anthranilate as substrates. Our results indicated that a single enzyme (PhnI) was responsible for the initial attack of a range of PAHs, including chrysene, in strain CHY-1. Furthermore, the conversion of salicylate to catechol was catalyzed by a three-component oxygenase unrelated to known salicylate hydroxylases.

Amino Acid Sequence↗