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 919 records · Page 51Linked to original sources
PubMed1986

Organization of the functional domains of anthranilate synthase from Neurospora crassa. Limited proteolysis studies.

Treatment of the multifunctional alpha 2 beta 2 anthranilate synthase complex of Neurospora crassa with elastase produced two fragments of the complex, one possessing anthranilate synthase activity and the other having both indole-3-glycerol phosphate (InGP) synthase and N-(5'-phosphoribosyl)anthranilate (PRA) isomerase activities. Sequencing the NH2 terminus of the InGP synthase-PRA isomerase fragment revealed that cleavage was between positions 237 and 238 of the beta-subunit within a segment of the polypeptide chain which links the glutamine-binding (G) domain with the InGP synthase-PRA isomerase domains. The fragment containing anthranilate synthase activity has a molecular weight of 98,000, as estimated by gel filtration, and is composed of an apparently intact alpha-subunit (70 kDa) associated with the G-domain fragment (29 kDa) derived from the beta-subunit. The alpha X G-domain complex was resistant to further degradation by elastase. When either the alpha 2 beta 2 complex or the alpha X G-domain complex was incubated with trypsin, the alpha-subunit was degraded to a 66-kDa alpha-fragment with reduced enzymatic activity, which was resistant to further cleavage. In contrast, incubation of alpha-subunit alone with either elastase or trypsin resulted in its complete degradation, indicating that association of the alpha-subunit with either G-domain or beta-subunit protected the alpha-subunit from this extensive degradation. A model for the anthranilate synthase complex is proposed in which the trifunctional beta-subunit forms a dimer by the self-association of the InGP synthase-PRA isomerase domains; the G-domain is connected to the InGP synthase-PRA isomerase domain by a relatively disordered region of the peptide chain which, in the alpha 2 beta 2 complex, remains susceptible to proteases; and neither alpha-subunit nor G-domain significantly self-associates.

Amino Acid Sequence↗
PubMed1990

Sunscreening agent intolerance: contact and photocontact sensitization and contact urticaria.

Reports in the literature of sensitization associated with many commonly used sunscreening agents including p-aminobenzoic acid (PABA), PABA derivatives, anthranilates, salicylates, cinnamates, benzophenones, and dibenzoylmethane derivatives are reviewed. Several of these case reports involved subjects with various photodermatoses, implicating enhanced sensitivity of the patient's skin to both light and chemicals. Despite the widespread use of sunscreens, the small number of published reports of contact and photocontact sensitization to these agents suggests that either such sensitization is less than commonly perceived or is underreported. Establishment of a registry for reporting adverse effects associated with sunscreening agents would help to characterize the incidence of sensitization.

4-Aminobenzoic Acid↗
PubMed2004

In vitro reconstitution of rice anthranilate synthase: distinct functional properties of the alpha subunits OASA1 and OASA2.

Anthranilate synthase (AS) is a key enzyme in the biosynthesis of various indole compounds including tryptophan. AS consists of two subunits, alpha and beta, and converts chorismate to anthranilate. Two or more AS alpha-subunit genes have been identified and characterized in several land plants. Although alpha subunits of AS induced by elicitation have been suggested to play significant roles in secondary metabolism, the biochemical and precise functional properties of individual AS isozymes have remained unclear. We have previously identified and characterized two AS alpha-subunit genes (OASA1 and OASA2) in rice (Oryza sativa ). To provide further insight into the enzymatic functions of AS isozymes in rice, we have now isolated rice cDNAs encoding the AS beta subunits OASB1 and OASB2 and reconstituted AS isozymes in vitro with the wheat germ cell-free system for protein expression. Both OASB subunits conferred glutamine-dependent AS activity on either OASA1 or OASA2, indicating the absence of a marked functional difference between the two beta subunits in terms of amidotransferase activity. Furthermore, both OASA subunits required assembly with a beta subunit to achieve maximal enzymatic activity even with NH(4)(+) as the amino donor. The V (max) and K (i) for tryptophan of the OASA1-OASB1 isozyme with glutamine as the amino donor, however, were 2.4 and 7.5 times, respectively, those of OASA2-OASB1, suggesting that AS isozymes containing OASA1 possess a higher activity and are less sensitive to feedback inhibition than those containing OASA2. Our biochemical characterization of reconstituted AS isozymes has thus revealed distinct functional properties of these isozymes in rice.

Amino Acid Sequence↗
PubMed2002

Structural analysis of two enzymes catalysing reverse metabolic reactions implies common ancestry.

The crystal structure of the dimeric anthranilate phosphoribosyltransferase (AnPRT) reveals a new category of phosphoribosyltransferases, designated as class III. The active site of this enzyme is located within the flexible hinge region of its two-domain structure. The pyrophosphate moiety of phosphoribosylpyrophosphate is co-ordinated by a metal ion and is bound by two conserved loop regions within this hinge region. With the structure of AnPRT available, structural analysis of all enzymatic activities of the tryptophan biosynthesis pathway is complete, thereby connecting the evolution of its enzyme members to the general development of metabolic processes. Its structure reveals it to have the same fold, topology, active site location and type of association as class II nucleoside phosphorylases. At the level of sequences, this relationship is mirrored by 13 structurally invariant residues common to both enzyme families. Taken together, these data imply common ancestry of enzymes catalysing reverse biological processes--the ribosylation and deribosylation of metabolic pathway intermediates. These relationships establish new links for enzymes involved in nucleotide and amino acid metabolism.

Amino Acid Sequence↗
PubMed1995

Immunological characterization and chloroplast localization of the tryptophan biosynthetic enzymes of the flowering plant Arabidopsis thaliana.

In order to study the tryptophan biosynthetic enzymes of the plant Arabidopsis thaliana, polyclonal antibodies were raised against five of the tryptophan biosynthetic pathway proteins: anthranilate synthase alpha subunit, phosphoribosylanthranilate transferase, phosphoribosylanthranilate isomerase, and the tryptophan synthase alpha and beta subunits. Immunoblot analysis of Arabidopsis leaf protein extracts revealed that the antibodies identify the corresponding proteins that are enriched in Arabidopsis chloroplast fractions. Precursors of phosphoribosylanthranilate isomerase and tryptophan synthase alpha subunit were synthesized by in vitro translation. The precursors were efficiently imported and processed by isolated spinach chloroplasts, and the cleavage sites within the precursors were determined. These results provide the first direct evidence that the tryptophan biosynthetic enzymes from Arabidopsis are synthesized as higher molecular weight precursors and then imported into chloroplasts and processed into their mature forms.

Aldose-Ketose Isomerases↗
PubMed1998

Tissue culture-specific expression of a naturally occurring tobacco feedback-insensitive anthranilate synthase.

A cDNA and corresponding promoter region for a naturally occurring, feedback-insensitive anthranilate synthase (AS) alpha-subunit gene, ASA2, has been isolated from an unselected, but 5-methyl-tryptophan-resistant (5MTr), tobacco (Nicotiana tabacum) cell line (AB15-12-1). The ASA2 cDNA contains a putative transit peptide sequence, and Southern hybridization shows that more than one closely related sequence is present in the tobacco genome. The ASA2 cDNA complemented a trpE nonsense mutant Escherichia coli strain, allowing growth on 300 microm 5MT-containing minimal medium without tryptophan, and cell extracts contained feedback-insensitive AS activity. The 5MTr was lost when the E. coli strain was transformed with an ASA2 site-directed mutant (phenylalanine-107-arginine-108 --> serine-107-glutamine-108). Identical nucleotide sequences encoding the phenylalanine-107-arginine-108 region have been found in polymerase chain reaction-amplified 326-bp ASA2 genomic fragments of wild-type (5-methyl-tryptophan-sensitive [5MTs]) tobacco and a progenitor species. High-level ASA2 transcriptional expression was detected only in 5MTr-cultured cells, not in 5MTs cells or in plants. Promoter studies indicate that tissue specificity of ASA2 is controlled by the promoter region between -2252 and -607. Since the ASA2 promoter sequences are not substantially different in the 5MTr and 5MTs lines, the increased levels of ASA2 mRNA in the 5MTr lines are most likely due to changes in a regulatory gene affecting ASA2 expression.

Amino Acid Sequence↗
PubMed2004

Regulation of the tryptophan biosynthetic genes in Bacillus halodurans: common elements but different strategies than those used by Bacillus subtilis.

In Bacillus subtilis, an RNA binding protein called TRAP regulates both transcription and translation of the tryptophan biosynthetic genes. Bacillus halodurans is an alkaliphilic Bacillus species that grows at high pHs. Previous studies of this bacterium have focused on mechanisms of adaptation for growth in alkaline environments. We have characterized the regulation of the tryptophan biosynthetic genes in B. halodurans and compared it to that in B. subtilis. B. halodurans encodes a TRAP protein with 71% sequence identity to the B. subtilis protein. Expression of anthranilate synthetase, the first enzyme in the pathway to tryptophan, is regulated significantly less in B. halodurans than in B. subtilis. Examination of the control of the B. halodurans trpEDCFBA operon both in vivo and in vitro shows that only transcription is regulated, whereas in B. subtilis both transcription of the operon and translation of trpE are controlled. The attenuation mechanism that controls transcription in B. halodurans is similar to that in B. subtilis, but there are some differences in the predicted RNA secondary structures in the B. halodurans trp leader region, including the presence of a potential anti-antiterminator structure. Translation of trpG, which is within the folate operon in both bacilli, is regulated similarly in the two species.

Amino Acid Sequence↗
PubMed1983

The nucleotide sequence of the first externally suppressible--1 frameshift mutant, and of some nearby leaky frameshift mutants.

Nine mutants within a 23 nucleotide sequence of the trpE gene of Salmonella typhimurium have been characterized. trpE91, a mutant which is externally suppressible has a single base deletion. Eight (or nine) nucleotides upstream of this deletion, two independently isolated mutations have the same transversion. In combination with trpE91 these mutations lead to partial restoration of synthesis of anthranilate synthetase in the absence of external suppressors. In the transversion the sequence A CA is changed to A AA and this new sequence may be the site where frameshifting occurs to allow leakiness. Leakiness is displayed by two further mutants of the same sign as trpE91, and one of the opposite sign, in the absence of any base substitution or external suppressors. Specific sequences, e.g., UUUC, may be especially prone to frameshifting and this sequence is created at the site of the +1 frameshift mutant which displays leakiness. In the new reading frame generated by the two -1 frame leaky mutants, a tryptophan codon is encountered. Leakiness is necessarily detected in the absence of tryptophan and under these conditions there will be a shortage of charged tryptophan tRNA. The possibility of such functional imbalance leading to frameshifting in these mutants is discussed.

Amino Acid Sequence↗
PubMed1999

The crystal structure of anthranilate synthase from Sulfolobus solfataricus: functional implications.

Anthranilate synthase catalyzes the synthesis of anthranilate from chorismate and glutamine and is feedback-inhibited by tryptophan. The enzyme of the hyperthermophile Sulfolobus solfataricus has been crystallized in the absence of physiological ligands, and its three-dimensional structure has been determined at 2.5-A resolution with x-ray crystallography. It is a heterotetramer of anthranilate synthase (TrpE) and glutamine amidotransferase (TrpG) subunits, in which two TrpG:TrpE protomers associate mainly via the TrpG subunits. The small TrpG subunit (195 residues) has the known "triad" glutamine amidotransferase fold. The large TrpE subunit (421 residues) has a novel fold. It displays a cleft between two domains, the tips of which contact the TrpG subunit across its active site. Clusters of catalytically essential residues are located inside the cleft, spatially separated from clustered residues involved in feedback inhibition. The structure suggests a model in which chorismate binding triggers a relative movement of the two domain tips of the TrpE subunit, activating the TrpG subunit and creating a channel for passage of ammonia toward the active site of the TrpE subunit. Tryptophan presumably blocks this rearrangement, thus stabilizing the inactive states of both subunits. The structure of the TrpE subunit is a likely prototype for the related enzymes 4-amino 4-deoxychorismate synthase and isochorismate synthase.

Amino Acid Sequence↗
PubMed1988

Molecular cloning and nucleotide sequence of Thermus thermophilus HB8 trpE and trpG.

The trpE gene of Thermus thermophilus HB8 was cloned by complementation of an Escherichia coli tryptophan auxotroph. The E. coli harboring the cloned gene produced the anthranilate synthase I, which was heat-stable and enzymatically active at higher temperature. The nucleotide sequence of the trpE gene and its flanking regions was determined. The trpE gene was preceded by an attenuator-like structure and followed by the trpG gene, with a short gap between them. No other gene essential for tryptophan biosynthesis was observed after the trpG gene. The amino-acid sequences of the T. themophilus anthranilate synthase I and II deduced from the nucleotide sequence were compared with those of other organisms.

Amino Acid Sequence↗
PubMed1982

Some new 2-aryloxymethyl-3-alpha-substituted carboxymethyl-6,8-substituted-4-quinazolones as possible anticonvulsants.

In view of their expected MAO inhibitory, CNS depressant and anticonvulsant properties, thirty new 2-aryloxymethyl-3-alpha-substituted carboxymethyl-6,8-substituted-4-quinazolones were synthesized by the reaction of substituted anthranil with various amino acids in pyridine. Some of these compounds at a concentration of 1 X 10(-3) mol/l inhibited rat brain monamine oxidase (MAO) in vitro and provided protection against pentylenetetrazole induced convulsions in mice.

Animals↗
PubMed1992

Protein folding within the cell is influenced by controlled rates of polypeptide elongation.

Previous studies have proposed that specific translational pauses have evolved to promote protein folding inside the cell by temporally separating the folding of specific regions of some polypeptide chains during their synthesis. Here we show that this is the case for a bifunctional protein in Saccharomyces cerevisiae. The yeast TRP3 gene contains a translational pause comprising ten contiguous non-preferred codons within its second functional domain (indoleglycerol phosphate synthase). Site-directed mutagenesis was used to remove this translational pause by increasing the codon bias of the region without changing the amino acid sequence of the protein (to create the gene TRP3pr: pause replaced). The TRP3pr gene was able to complement a trp3:: URA3 null mutation in yeast. No significant differences in the doubling times of TRP3 or TRP3pr yeast transformants were observed during growth at 25 degrees C, 30 degrees C or 37 degrees C, or in the presence of sublethal concentrations of the analogue, 5-methyltryptophan. However, further analysis of TRP3 and TRP3pr transformants revealed that the removal of the translational pause causes a 1.5-fold decrease in indoleglycerol phosphate synthase activity per TRP3 mRNA. This observation which is statistically significant (P < 0.05) and reproducible, suggests that translational pausing promotes the correct intracellular folding of the TRP3 protein.

Amino Acid Sequence↗
PubMed1989

Occurrence of bilirubin-IX beta in the gallbladder bile of eel, Anguilla japonica.

Bilirubin-IX beta isomer was detected in the bile of eel, Anguilla japonica, as evidenced by high-performance liquid chromatography (HPLC) analysis of free acid and its ethyl anthranilate diazo derivatives. Bilirubin-IX beta accounted for 16.7 +/- 6.0 (mean +/- S.D.) percent of the total bilirubins in the bile of 40 eels analysed, and the percentage was much higher than that reported in the biles of mammals.

Anguilla↗
PubMed1984

Nucleotide sequence of the Bacillus subtilis trpE and trpD genes.

Several overlapping portions of the tryptophan (trp) operon of Bacillus subtilis have been cloned into plasmid pBR322. The nucleotide sequence of the region comprising the trpE and trpD genes and a portion of the trpC gene has been determined. When the deduced amino acid sequences of these genes are compared with their counterparts in Escherichia coli, several regions of striking homology are seen. The probable initiation codons for the trpE, D and C genes are each preceded by a recognizable Shine-Dalgarno sequence. The coding sequences for the trpE and trpD genes and for the trpD and trpC genes overlap slightly, leaving no intercistronic regions between the genes.

Amino Acid Sequence↗
PubMed1998

A Myb homologue, ATR1, activates tryptophan gene expression in Arabidopsis.

In Arabidopsis thaliana, tryptophan pathway genes are induced in response to starvation, wounding, and pathogen attack, resulting in increased production of tryptophan and secondary metabolites important for development and defense. The Arabidopsis tryptophan pathway therefore provides an ideal system for elucidating how environmental stimuli are transduced into changes in plant gene expression. To characterize the factors that regulate the first gene in the pathway, ASA1, which is the key point of control, we have isolated altered tryptophan regulation (atr) mutants with deregulated expression of ASA1. One of these mutants, atr1D is dominant for increased transcription of ASA1 in specific seedling tissues. We have used atr1D to clone the ATR1 gene based on its map position. ATR1 encodes a Myb-like transcription factor that modulates ASA1 expression. The ATR1 transcript also includes a 5' regulatory region with three short ORFs, one of which is prematurely terminated by the atr1D mutation. Thus, ATR1 defines the first characterized tryptophan gene regulator in plants, and the atr1D mutation defines a sequence important for ATR1 expression.

Amino Acid Sequence↗
PubMed1996

Amino acid and adenine cross-pathway regulation act through the same 5'-TGACTC-3' motif in the yeast HIS7 promoter.

The HIS7 gene of Saccharomyces cerevisiae encodes a bifunctional glutamine amidotransferase:cyclase catalyzing two reactions that lead to the formation of biosynthetic intermediates of the amino acid histidine and the purine adenine. The HIS7 gene is activated by GCN4p under environmental conditions of amino acid starvation through two synergistic upstream sites GCRE1 and GCRE2. The BAS1p-BAS2p complex activates the HIS7 gene in response to adenine limitation. For this activation the proximal GCN4p-binding site GCRE2 is required. GCN4p and BAS1p bind to GCRE2 in vitro. Under conditions of simultaneous amino acid starvation and adenine limitation the effects of GCN4p and BAS1/2p are additive and both factors are necessary for maximal HIS7 transcription. These results suggest that GCN4p and BAS1/2p are able to act simultaneously through the same DNA sequence in vivo and use this site independently from each other in a non-exclusive manner.

Acyltransferases↗