Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interferons can induce neopterin biosynthesis and tryptophan degradation in monocytic cells. Indoleamine 2,3-dioxygenase (IDO), an inducible cellular enzyme, metabolizes tryptophan to N-formyl-L-kynurenine. Tryptophan degradation has been linked to interferon-mediated inhibition of replication by intracellular pathogens and inhibition of cancer cell proliferation. We evaluated the ability of the recombinant human interferons beta ser and gamma to stimulate neopterin production and tryptophan degradation in vitro by alveolar macrophages (AM) obtained from normal volunteers by bronchoalveolar lavage. Additionally, because other biologic response modifiers such as lipopolysaccharide (LPS) can also stimulate monocytic cells to produce increased amounts of neopterin and degrade tryptophan, we evaluated the effects of LPS on interferon-induced neopterin production and tryptophan degradation by AM. Both interferon-gamma (IFN-gamma) and interferon-beta (IFN-beta) induced neopterin production and tryptophan degradation by AM with corresponding inhibition of intracellular replication by Chlamydia psittaci in AM, but IFN-gamma was a more potent inducer of these responses than IFN-beta. LPS enhanced neopterin production and tryptophan degradation by interferon-exposed cells. This effect was particularly evident at lower concentrations of interferon, and LPS synergy was more pronounced with IFN-beta than IFN-gamma. Concentrations of LPS that alone had no stimulatory effect on tryptophan degradation synergistically enhanced the induction of IDO activity by lower concentrations of interferon. These studies suggest that IFN-gamma stimulates human AM to produce neopterin and degrade tryptophan more potently than IFN-beta, and that low concentrations of LPS can synergistically enhance such effects of interferons on tissue macrophage metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1992 Jun
PMID:Effects of interferons beta or gamma on neopterin biosynthesis and tryptophan degradation by human alveolar macrophages in vitro: synergy with lipopolysaccharide. 159 Oct 13

The enzyme tryptophan decarboxylase (TDC) (EC 4.1.1.28) converts tryptophan into tryptamine, and thereby channels primary metabolites into indole alkaloid biosynthesis. The production of these secondary metabolites in suspension cells of Catharanthus roseus depends on medium composition. Of the possible variables, we investigated the effect of hormones on the expression of the tdc gene in cell cultures. Omission of NAA from the growth medium resulted in accumulation of tdc mRNA. The addition of 1-naphthaleneacetic acid (NAA), indoleacetic acid (IAA) or 2,4-dichlorophenoxyacetic acid (2,4-D) rapidly reduced the enhanced tdc transcript level. Cytokinin was unable to suppress the enhanced transcript level. Hairy roots transformed by Agrobacterium rhizogenes also showed a reduction of the tdc mRNA level after NAA addition. Run-off transcription experiments showed that the down-regulation takes place at the transcriptional level within 15 minutes and independent of de novo protein synthesis. Thus one of the mechanisms which control the activity of terpenoid indole alkaloid biosynthesis in C. roseus cell cultures is the negative regulation by auxin of the gene involved in the first committed step.
Plant Mol Biol 1992 Apr
PMID:Auxin rapidly down-regulates transcription of the tryptophan decarboxylase gene from Catharanthus roseus. 160 Jan 47

The six clones pTB112, pTB324, pTBs12, pCd122, pCd14 and pCd13 cover the tox locus of Clostridium difficile VPI 10463. This region of 19 kb of chromosomal DNA contains four open reading frames including the complete toxB and toxA genes. The two toxins show 63% amino acid (aa) homology, a relatedness that had been predicted by the cross-reactivity of some monoclonal antibodies (mAb) but that is in contrast to the toxin specificity of polyclonal antisera. A special feature of ToxA and ToxB is their repetitive C-termini. We define herein 19 individual CROPs (combined repetitive oligopeptides of 20-50 aa length) in the ToxB C-terminus, which are separable into five homologous groups. Comparison of the aa sequences of the N-terminal two-thirds of ToxA and ToxB revealed three marked structures, a cluster of 172 hydrophobic, highly conserved aa in the centre of both toxins, a sequence of 120 residues with an accumulation of highly conserved arginine, cysteine, histidine, methionine, and tryptophan residues, and a stretch of 248 less conserved aa. The probable function of these domains is discussed. Structural and functional homologies of ToxA and ToxB indicate that both genes have a common ancestor and may have evolved by gene duplication, with subsequent recombination and mutation, as has been reported for streptococcal glucosyltransferases (Gtf).
Mol Gen Genet 1992 May
PMID:Comparative sequence analysis of the Clostridium difficile toxins A and B. 160 68

We have refined the 1.9 A resolution crystal structures of two maltodextrin receptor mutants in which tryptophan residues 230 and 232 have been changed to alanine and compared these structures with the refined 1.7 A structure of the wild-type protein. In the wild-type structure, Trp230, which is located in the maltodextrin-binding groove, stacks against the B-face of the reducing sugar of the bound maltose. Trp232, which is located near the protein surface, does not participate directly in sugar binding. Relative to the wild-type structure, neither mutation caused a significant rearrangement in the overall protein structure or in the mode of binding maltose. Although the position once occupied by Trp230 remains empty, a new water molecule has moved near the void. In contrast, a new water molecule has entered into the space once occupied by Trp232. Whereas one hydrogen bond is formed with the water molecule near the Trp230 void, no hydrogen bond is associated with the water molecule occupying the space vacated by Trp232. The three van der Waals' contacts between Trp230 and maltose in the wild-type structure that are lost in the W230A mutation could contribute to the 12-fold decrease in ligand-binding activity of the mutant protein. The W232A mutation causes little change in binding activity. The structures of these mutant proteins also provide some insight into the complicated tryptophan fluorescence spectra of the maltodextrin binding-protein. The change in fluorescence due to the deletion of Trp230 can readily be explained as resulting directly from loss of Trp230 in the sugar-binding site. The change in fluorescence due to deletion of Trp232, however, is ascribed to the modification of local interactions mediated by the binding of maltodextrin since the tryptophan is not directly involved in any sugar-binding interaction.
J Mol Biol 1992 Jul 05
PMID:Atomic interactions in protein-carbohydrate complexes. Tryptophan residues in the periplasmic maltodextrin receptor for active transport and chemotaxis. 161 48

A gene encoding a proto-oncogene, a myb-related gene named Atmyb1, was cloned from Arabidopsis thaliana, and its nucleotide sequence was determined. The Atmyb1 gene contains an intron of 494 bp, and there are no highly homologous sequences present in the A. thaliana genome, but evidence was found that other myb-related genes exist. In the 5' flanking region, we found several typical cis-acting elements found in plant promoters. Sequence comparisons revealed that the ATMYB1 protein has a putative DNA-binding domain with two repeats of tryptophan clusters, which is common in MYB-related proteins in plants, while animal MYB-related proteins contain DNA-binding domains with three repeats of tryptophan clusters. The putative DNA-binding domain of the ATMYB1 protein has higher homology with that of the human c-MYB protein than with those of other plant MYB proteins.
Plant Mol Biol 1992 Jun
PMID:Nucleotide sequence of a gene from Arabidopsis thaliana encoding a myb homologue. 162 93

Alpha interferon stimulates transcription by converting the positive transcriptional regulator ISGF3 from a latent to an active form. This receptor-mediated event occurs in the cytoplasm, with subsequent translocation of the activated factor to the nucleus. ISGF3 has two components, termed ISGF3 alpha and ISGF3 gamma. ISGF3 gamma serves as the DNA recognition subunit, while ISGF3 alpha, which appears to consist of three polypeptides, is a target for alpha interferon signaling and serves as a regulatory component whose activation is required to form ISGF3. ISGF3 gamma DNA-binding activity was identified as a 48-kDa polypeptide, and partial amino acid sequence has allowed isolation of cDNA clones. ISGF3 gamma translated in vitro from recombinant clones bound DNA with a specificity indistinguishable from that of ISGF3 gamma purified from HeLa cells. Sequencing of ISGF3 gamma cDNA clones revealed significant similarity to the interferon regulatory factor (IRF) family of DNA binding proteins in the amino-terminal 117 residues of ISGF3 gamma. The other IRF family proteins bind DNA with a specificity related to but distinct from that of ISGF3 gamma. We note sequence similarities between the related regions of IRF family proteins and the imperfect tryptophan repeats which constitute the DNA-binding domain of the c-myb oncoprotein. These sequence similarities suggest that ISGF3 gamma and IRF proteins and the c-myb oncoprotein use a common structural motif for DNA recognition. Recombinant ISGF3 gamma, like the natural protein, interacted with HeLa cell ISGF3 alpha to form the mature ISGF3 DNA-binding complex. We suggest that other IRF family members may participate in signaling pathways by interacting with as yet unidentified regulatory subunits analogous to ISGF3 alpha.
Mol Cell Biol 1992 Aug
PMID:Subunit of an alpha-interferon-responsive transcription factor is related to interferon regulatory factor and Myb families of DNA-binding proteins. 163 Apr 47

5-Lipoxygenase-activating protein (FLAP) is specifically labeled by [125I]L-669,083 and [125I]L-691,678, photoaffinity analogues of two classes of potent leukotriene biosynthesis inhibitors. Because human FLAP contains only a single tryptophan residue at position 72 and two internal methionine residues at positions 89 and 125, we have used reagents that specifically cleave at these residues, in conjunction with antipeptide antisera, to localize the site of attachment of the photoaffinity ligands. Immunoprecipitation of specifically labeled peptide fragments after digestion of photoaffinity-labeled FLAP by iodosobenzoic acid at 72Trp demonstrates that the inhibitors bind to FLAP amino-terminal to this residue. This finding is consistent with similar immunoprecipitation studies after digestion at methionine residues using cyanogen bromide. These findings localize the site of attachment of the inhibitors to a region of FLAP that includes the hydrophilic loop between the proposed first and second transmembrane regions. Based on these findings, site-directed mutagenesis of human FLAP was performed to define key amino acids involved in inhibitor binding. Using a radioligand binding assay, analysis of mutants of human FLAP expressed in COS-7 cells demonstrates that a number of residues in the amino-terminal half of the first hydrophilic loop of the protein can be deleted without significantly affecting inhibitor binding. In contrast, no inhibitor binding was detectable with mutants in which amino acid residues in the carboxyl-terminal half of this loop were deleted. Furthermore, a point mutation of 62Asp to asparagine results in a mutant with dramatically reduced affinity for inhibitors. This loss of affinity was not displayed by a mutant in which 62Asp was mutated to a glutamate residue, suggesting that a negative charge associated with residue 62 may be critical for inhibitor binding. The roles that amino acid residues in the carboxyl-terminal half of the first hydrophilic loop of FLAP may play in the binding of leukotriene biosynthesis inhibitors are currently under investigation.
Mol Pharmacol 1992 Jul
PMID:Identification of amino acid residues of 5-lipoxygenase-activating protein essential for the binding of leukotriene biosynthesis inhibitors. 163 56

Spontaneous and chemically induced revertant colonies were not observed on plates when a strictly anaerobic environment and anaerobically prepared media were used to perform the Ames histidine reversion assay with each of eight different Salmonella strains. A similar effect was observed when the E. coli tryptophan reverse mutation assay was performed under strictly anaerobic conditions. We provide evidence here that under anaerobic conditions growth inhibitor(s) are formed by the S. typhimurium and E. coli bacteria when the limited histidine and tryptophan, respectively, are depleted from the medium. The inhibitor(s) are nonspecific and inhibit the growth not only of prototrophic bacteria but also of the inhibitor-producing bacteria as measured by neutralized supernatants of growth-limiting minimal liquid cultures. Inhibitor(s) are also formed in stationary phase cultures of Salmonella and E. coli in minimal liquid medium supplemented with excess histidine and tryptophan, respectively. These results suggest that inhibitor formation under anaerobic conditions is a physiological phenomenon which interferes with at least two reverse mutation assays. Whether or not it also interferes with the reverse mutagenesis process remains to be determined.
Environ Mol Mutagen 1992
PMID:Evidence that inhibitor(s) are formed which may interfere with the growth of revertant colonies in the Ames Salmonella and the E. coli tryptophan reverse mutation assays when strictly anaerobic conditions are used. 163 83

Activation of tyrosine and tryptophan hydroxylases, key enzymes for the catecholamine and serotonin biosynthesis, requires Ca2+/calmodulin-dependent protein kinase II and 14-3-3 protein which comprises a family of, at least, seven polypeptides in the bovine. Here we show that the amino acid sequence of the rat 14-3-3 eta chain deduced from the nucleotide sequence is completely identical to that of bovine counterpart. Using in situ hybridization the expression of mRNA for this protein is detected not only in the monoamine-synthetic neurons but also in many other discrete nuclei which synthesize neither catecholamine nor serotonin. The highly conservative structure between mammalian species and wider expression of this protein than expected in the central nervous system suggest that the 14-3-3 protein exerts some, though yet to be defined, functions fundamental to neuronal activities other than activation of the monoamine biosynthesis.
Brain Res Mol Brain Res 1991 May
PMID:Molecular cloning of cDNA to rat 14-3-3 eta chain polypeptide and the neuronal expression of the mRNA in the central nervous system. 164 68

We have cloned and analyzed the sugar-beet mitochondrial gene for cytochrome oxidase subunit II (coxII). The sugar-beet and its deduced amino acid sequence were compared to its homologous coxII gene sequences from both monocot and dicot plants. It was found to be highly conserved (89-95%) compared to homologue in other plant species. The 780 bp coding sequence of the sugar beet coxII gene is interrupted at position 383 by a 1463 bp intron. This intron contains an additional 107 bp sequence that is not found in any of the plant coxII genes studied thus far. The structure of the intron suggests that a large intron existed in an ancestral coxII gene before monocots and dicots diverged in evolution. Three CGG codons in the sugar-beet coxII coding sequence align with conserved tryptophan residues in the homologous gene of other species, suggesting that RNA editing takes place also in sugar-beet mitochondria. In 13 out of 24 codons of coxII mRNA that were found to be edited in four other plants, the sugar-beet gene already utilizes the edited codons. This phenomenon may indicate that the mitochondrial genome in sugar-beet is phylogenetically more archaic relative to these plants. An additional sequence of 279 bp that is identical to the first exon of coxII was identified in the mtDNA of the sugar-beet. This 'pseudo-gene' is transcribed and its existence in the mitochondrial genome is unexplained.
Plant Mol Biol 1991 Sep
PMID:The cytochrome oxidase II gene in mitochondria of the sugar-beet Beta vulgaris L. 165 62


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