Disease relevance of tryptophan radical

• Control experiments established that oligomers that were not complementary to E. coli trp leader RNA did not affect attenuation and that the 15-mer did not reduce termination when the transcript lacked a complementary region [1].
• In a highly purified DNA-dependent peptide-synthesizing system, synthesis of the di- and tripeptides predicted from the Salmonella typhimurium trp operon leader sequence, fMet-Ala and fMet-Ala-Ala, also was observed [2].
• Wild-type and translation-defective trp leader templates of E. coli and Serratia marcescens were employed, and pause RNA synthesis and paused complex release (activation) were quantified relative to synthesis of the terminated leader transcript [3].
• TRAP (trp RNA-binding attenuation protein) is an 11 subunit RNA-binding protein that regulates expression of genes involved in tryptophan metabolism (trp) in Bacillus subtilis in response to changes in intracellular tryptophan concentration [4].
• Cloning of the trp gene cluster from a tryptophan-hyperproducing strain of Corynebacterium glutamicum: identification of a mutation in the trp leader sequence [5].

Psychiatry related information on tryptophan radical

• Low levels of Trp lead to decrease of serotonin synthesis, which is likely to be related to the depressive symptoms [6].

High impact information on tryptophan radical

• Recombinantly expressed TrpRS II binds tryptophan (Trp), ATP, and D. radiodurans tRNA(Trp) and catalyzes the formation of 5' adenyl-Trp and tRNA(Trp), with approximately five times less activity than TrpRS I [7].
• Translation activates the paused transcription complex and restores transcription of the trp operon leader region [3].
• These findings indicate that the paused trp leader transcription complex resumes transcription when released by ribosome movement over the leader peptide coding region [3].
• However, distal nucleotide sequences also seem to play a role in modulating termination at trp t [8].
• In vivo the mutants have 2- to 4-fold increased levels of expression of the trp operon above the level of the trpR parental strain [9].

Chemical compound and disease context of tryptophan radical

• We have isolated two regulatory mutants altered in the leader region of the Escherichia coli tryptophan (trp) operon [10].

Biological context of tryptophan radical

• Using this dipeptide synthesis system, we demonstrated that translation initiation at the ribosome binding site used for trp leader peptide synthesis was reduced 10-fold when the transcript contained a segment complementary to the ribosome binding site [2].
• Transcription proceeding past the trp attenuator of this plasmid terminates at this new terminator sequence and results in the production of a approximately 400-nucleotide long read-through transcript [11].
• We studied the dependence of pausing on hairpin stability by examining mutant trp templates containing base pair substitutions in the region corresponding to the hairpin secondary structure [12].
• GST-ASA1 cleavage by thrombin, as well as site-directed mutagenesis modifications of the Trp allosteric site, inactivated the recombinant protein [13].
• The unusual temperature dependence is fitted by a phenomenological two-state model in which the phosphorescence originates primarily from a donor, tryptophan (Trp) 104, and an acceptor, Trp 60, the populations of which are coupled by a thermally activated triplet-triplet energy transfer process [14].

Anatomical context of tryptophan radical

• T cell inhibition is achieved through both TRP depletion and TRP metabolite accumulation in specific local tissue microenvironments [15].
• The supplementation of alpha LA resulting in a higher TRP supply to low-protein diets is a further step towards the production of infant formulas more closely adapted to human breast milk [16].
• In macrophages, IFN-gamma strongly induces indoleamine (2,3)-dioxygenase, an enzyme which degrades tryptophan (trp) to kynurenine (kyn) [17].
• On the basis of these observations we tried to examine whether one of the TRP metabolites, anthranilic acid (AA), shows interaction with membranes of erythrocytes and because of that it may contribute to anaemia development [18].

Associations of tryptophan radical with other chemical compounds

• In fact, transcription of the trp leader region in vitro results in the fomration of a stable termination complex which can be observed on sucrose gradients or by binding to nitrocellulose filters [19].
• Horse metmyoglobin, which lacks Tyr-151 of the sperm whale protein, forms an oxygen-reactive tryptophanyl radical and also a phenoxyl radical at Tyr-103 [20].
• The Vmax (45 nmol min-1mg-1), the apparent K(M) for chorismate (180 microM), and the feedback inhibition by Trp (complete inhibition by 10 microM Trp) of the purified fusion product (GST-ASA1) were comparable to anthranilate synthase purified from plants [13].
• METHODS: The concentration of TRP and the break-down product kynurenine were measured by high-performance liquid chromatography in- and off-season in sera from patients with seasonal allergic rhinitis (n=12) and from clinically asymptomatic atopic patients sensitized to specific aeroallergens (n=12) [15].
• We found computational evidence suggesting that ferrous NOS is favored in wild-type NOS when compared to the Trp mutant, consistently with the fact that Trp mutants have been shown to accumulate less Fe(+2)-NO dead end species [21].

Gene context of tryptophan radical

• We constructed plasmid pAtrp46 in which lacZ gene expression is regulated by the attenuator of the Escherichia coli tryptophan (trp) operon [22].
• 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 [23].
• Analysis of attenuation by measurement of trp mRNA synthesis was facilitated by constructing a plasmid (pAD1) containing the rpoC transcription terminator inserted early in trpE [11].
• Introduction of these rpoB mutations into mutant strains which terminate transcription abnormally at the trp operon attenuator established that the rpoB mutations alter trp operon expression by increasing or decreasing transcription termination at the attenuator [24].
• We conclude that during transcription of the trp operon RNA polymerase frequently is rejected at a specific site ahead of the first structural gene, trpE [25].

Analytical, diagnostic and therapeutic context of tryptophan radical

• The length of trp regRNA determined by filtration on Sephadex G-200 is 110-180 nucleotides [25].
• To study the effect of alpha LA-enrichment on the TRP supply, cross-over studies were carried out in 20 healthy infants up to 3 months of age [16].
• Using EPR with spin-trapping, the tryptophanyl radical, generated by either method was found to react with oxygen, although this reaction is too slow to be observed by pulse radiolysis (k < 5 x 10(6) dm3 mol-1 s-1) [26].
• Serum TRP levels of the formula-fed infants with the higher TRP content did not differ significantly from an exclusively breastfed control group of 11 infants (10.5 +/- 4.8 versus 10.9 +/- 4.7 mg l-1, p = 0.841), whereas levels of the formula-fed infants with the moderate TRP content were significantly lower (7.4 +/- 3.9, p = 0.038) [16].
• METHODS: FPLC size exclusion chromatography, far- and near-ultraviolet circular dichroism, and tryptophan (Trp) and 1-anilino-8-naphthalenesulfonate (ANS) fluorescence were used to study conformational change [27].

References