Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.1 (aspartate aminotransferase)
 21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The location, orientation and dynamics of a thiazole-containing analogue of distamycin 1 bound to the decadeoxyribonucleotide d-[CGCAATTGCG]2 have been studied by non-exchangable and imino proton NMR resonances of the 1:1 complex. Using NOE difference, COSY and NOESY experiments, lexitropsin (1) was located in the minor groove of DNA at 5'-CAAT sequence. This was concluded by an intermolecular NOE between the ligand and a minor groove A4H2 proton. The NOE cross-correlations in the NOESY map confirmed that the DNA decamer duplex in the 1:1 complex remains in a right-handed B-conformation similar to that in the free decamer. Experiments on non-exchangeable and exchangeable proton NMR resonances placed the N-formylamino terminus of drug 1 on the 5'-C3 nucleotide, while the rest of the molecule extends onto the 5'-AAT sequence. The structural evidence for sequence preferential binding at 5'CAAT rather than 5'AATT suggests this reflects an attempt on the part of the sterically demanding inward directed sulfur of the thiazole to minimize compression by moving part of the molecule to the somewhat wider CG base site. The lack of evidence for a 2:1 drug:DNA complex, in contrast to distamycin, is in accord with this interpretation. The lexitropsin 1 was found to be in an exchange between the equivalent 5'-CAAT sites at a rate of approximately 35S-1 with a delta G degree of 65 +/- 5 kJ mol-1 at 303 K. The experimental data suggests a slide-swing mechanism for this exchange process.
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PMID:Structural and dynamic aspects of non-intercalative (1:1) binding of a thiazole-lexitropsin to the decadeoxyribonucleotide d-[CGCAATTGCG]2: An 1H-NMR and molecular modeling study. 166 10

A complete cDNA encoding cholesterol 7 alpha-monooxygenase (EC 1.14.13.17) which had been isolated from rat liver cDNA libraries by using specific antibodies to the enzyme (Noshiro, M., Nishimoto, M., and Okuda, K. (1989) FEBS Lett. 257, 97-100) was totally sequenced. The cDNA contained a 1,509-base pair open reading frame encoding 503 amino acid residues (Mr = 56,880) and an unusually long 3'-untranslated region rich in AT sequence in the total length of 3,545 base pairs. The predicted amino acid sequence displays less than 30% similarity to other sequenced cytochrome P-450s indicating that the 7 alpha-hydroxylase constitutes a novel family of cytochrome P-450. The AT-rich region often contained ATTTA motifs, 5'-AAT-3' or 5'-TAA-3' trinucleotides which were reported to be involved in rapidly degrading mRNA. Employing the specific antibodies and the cDNA as probes, a diurnal variation of the levels of the three factors, i.e. enzyme protein, mRNA, and enzyme activity, was studied on rat livers prepared at various times of the day. In normal animals, all three factors exhibited maximum level at 10:00 p.m. and minimum at 10:00 a.m. No significant sexual difference was observed. Cholestyramine feeding increased all three factors at 10:00 a.m. close to the maximum levels of the normal rats, but did not show a significant increase at 10:00 p.m. On the contrary, starvation markedly decreased all three factors either at 10:00 a.m. or at 10:00 p.m., while maintaining still the diurnal variation. A good correlation of the levels of mRNA to the enzyme activities and the protein levels demonstrates that pretranslational regulation is most likely a mechanism for the circadian rhythm of 7 alpha-hydroxylase. The marked diurnal fluctuation of the amount of protein and the level of mRNA also indicates their rapid turnover. The short half-life of mRNA could be correlated with the structure of the 3'-untranslated region of the mRNA characteristic of rapidly degrading mRNA, i.e. abundance of motif, AUUUA, and existence of 5'-AAU-3' or 5'-UAA-3' trinucleotides in single-stranded regions of the secondary structure.
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PMID:Rat liver cholesterol 7 alpha-hydroxylase. Pretranslational regulation for circadian rhythm. 169 13

No standardized assessment of aphasic symptoms for stroke patients in the acute phase has as yet been published in the German language. Current test batteries such as the AAT are too time-consuming and cannot be performed on severely impaired patients. A short test for the examination of aphasic and dysarthric symptoms has been developed which contains 7 subtests in three main areas: spontaneous speech, comprehension and planning of movements, speech and language abilities. Since abilities in acute cases may only be functionally impaired and often only detectable after stimulation, standardized stimulation is applied in most of the subtests. In this way it is possible to test acute stroke patients for aphasic and dysarthric symptoms. The course of recovery in a typical case is described.
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PMID:[A test for the detection of speech and language disorders in the acute phase after stroke. Development and clinical application]. 170 24

A not uncommon arrhythmia in cardiac orthotopic transplantation patients is sinus node dysfunction with chronotropic incompetence. This is a result of the surgical procedure that denervates the donor heart while the native sinus node may be normal but isolated in the remnant of the recipient atrial wall that serves as the anastomotic site. We were able to restore "normal sinus node function" in a heart transplant patient utilizing a bipolar single chamber pacemaker programmed to the triggered mode. A single unipolar active fixation lead was positioned in each atria. Both leads were connected to a bipolar AAT pulse generator utilizing a Y adaptator. The native atrium with its innervated intact sinus node effectively drove the donor atrium and thus the heart.
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PMID:Bipolar atrial triggered pacing to restore normal chronotropic responsiveness in an orthotopic cardiac transplant patient. 172 Nov 23

Cytotoxic T lymphocyte (CTL)-mediated cytolysis is induced via the interaction of the specific T-cell antigen receptor and the peptidic viral antigen associated with the major histocompatibility complex class I antigen. Here we demonstrate in vitro that lymphocytic choriomeningitis virus (LCMV) can escape the cytotoxic activity of LCMV-specific cloned CTLs by single amino acid changes within the recognized T-cell epitope defined by residues 275-289 of the LCMV glycoprotein [LCMV-GP-(275-289)]. LCMV-infected fibroblasts at a multiplicity of infection of 10(-3) exposed to virus-specific CTL at an effector-to-target cell ratio of 4:1 4 hr after infection was optimal for virus mutant selection. The selections were carried out with three LCMV-GP-(275-289)-specific CTL clones expressing T-cell antigen receptors containing the identical variable gene segments V alpha 4 and V beta 10 but different junctional regions; selection was also possible with LCMV-GP-(275-289)-specific cytotoxic polyclonal T cells. The most common escape mutation was an amino acid change of asparagine (AAT) to aspartic acid (GAT) at position 280; an additional mutation was glycine (GGT) to aspartic acid (GAT) at position 282. The results presented show that relevant point mutations within the T-cell epitope of LCMV-GP-(275-289) occur frequently and that they are selectable in vitro by CTLs.
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PMID:In vitro selection of lymphocytic choriomeningitis virus escape mutants by cytotoxic T lymphocytes. 172 16

We have isolated an alfalfa leaf cDNA clone that encodes aspartate aminotransferase (AAT, EC 2.6.1.1) by direct complementation of an Escherichia coli aspartate auxotroph with a plasmid cDNA library. DNA sequence analysis of the recombinant plasmid, pMU1, revealed that a 1514 bp cDNA was inserted in the correct orientation and in-frame with the start of the lacZ coding sequence in the vector, pUC18. The resulting fusion protein is predicted to be 424 amino acids in length with a molecular weight of 46387 Daltons. The cDNA-encoded protein has a characteristic pyridoxal phosphate attachment site motif and has substantial amino acid sequence homology to both animal and bacterial AATs. Plasmid pMU1 encodes an AAT with a Km for aspartate of 3.3 mM, a Km for 2-oxoglutarate of 0.28 mM, and a pH optimum between 8.0 and 8.5. Several lines of evidence including Western blot analysis, the isoelectric point of the encoded protein, and the effect of pH on the activity of the fusion protein, suggest that the cDNA encodes the isozyme AAT-1 rather than AAT-2. Northern blot analysis showed that the aat-1 clone hybridized to a 1.6 kb transcript present in alfalfa leaves, roots and nodules. The relative concentrations of aat-1 mRNA in these tissues were 1:2:5, respectively. Thus, transcription of aat-1 appears to be induced during nodule development. Southern blot analysis suggested that AAT-1 in alfalfa is encoded by either a single-copy gene or a small, multigene family.
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PMID:Isolation and analysis of a cDNA clone that encodes an alfalfa (Medicago sativa) aspartate aminotransferase. 175 49

We investigated the prevalence of mutations in the gene encoding the major insulin-responsive facilitative glucose transporter (GLUT4) in patients with non-insulin-dependent diabetes mellitus (NIDDM). All 11 exons of the GLUT4 gene from 30 British white subjects with NIDDM were amplified using the polymerase chain reaction and screened for nucleotide sequence variation using the single-stranded conformation polymorphism (SSCP) method. No variation between the study subjects was detected in exons 1-3, 4b-8, and 10. Variant SSCP patterns were detected in exons 4a and 9. SSCP variation in exon 4a was revealed by direct nucleotide sequencing to be due to a common silent polymorphism (AAC----AAT at Asn130). One NIDDM patient demonstrated a variant SSCP pattern in exon 9. This was caused by a point mutation (GTC----ATC) at codon 383, which leads to the conservative substitution of isoleucine for valine in the putative fifth extracellular loop of the transporter. Allele-specific oligonucleotide hybridization was used to examine the frequency of this mutation in 240 Welsh white subjects (160 with NIDDM and 80 controls). The Val----Ile383 mutation was found in the heterozygous state in two diabetic subjects and no control subjects. We conclude that mutations of the GLUT4 coding sequence are very uncommon in this population of subjects with typical NIDDM. Determining whether the Ile383 GLUT4 variant present in 3 diabetic subjects contributes in any way to their disease will require further study.
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PMID:Molecular scanning of insulin-responsive glucose transporter (GLUT4) gene in NIDDM subjects. 175 12

We have studied the binding of echinomycin to DNA fragments containing GC-rich regions flanked by blocks of alternating AT by DNase I footprinting and diethylpyrocarbonate modification. Regions of alternating AT flanking the sequences CCCG, CCGC, CGGC and GG show a four base pair DNase I cleavage pattern and reaction of alternate adenines with diethylpyrocarbonate. This pattern is strongest when the AT-block is immediately adjacent to the CpG ligand binding site. We explain these phenomena by suggesting that echinomycin binds to the dinucleotide step ApT in a cooperative fashion. The cooperative effects can be transmitted through the dinucleotide step GC but not CC or AA. No such repetitive patterns are seen with surrounding regions of (ATT).(AAT). Evidence is presented for secondary drug binding sites at CpC and TpG with weaker interaction at the CpG site within the hexanucleotide TTCGAA.
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PMID:Echinomycin binding to alternating AT. 176 3

2.0 kb Hind III fragment isolated from cytoplasmic male-sterile carrot mitochondria, designated PKT5, was hybridized to ORF13 which is the coding region of a unique polypeptide in maize CMS (Dewey et al., 1986). Sequence analysis indicated that PKT5 is consisted of 3 domains. Domain 1 was identical to the 5'-flanking region of atp6 in maize CMS-TURF2H3 sequence (Dewey et al., 1986). Domain 2 contained a novel ORF encoding 72 amino acids, which was extremely homologous to the amino-terminal 67 amino acids of the unique ORF13 in maize CMS. Domain 3 except an amino acid change (Ile87 = ATT for Asn87 = AAT), was identical to ORF25 polypeptide in maize CMS. Connective sequences of these 3 domains were also highly homologous to the maize CMS-TURF2H3 sequence. Out of 7 recombination points in maize CMS-TURF2H3 sequence, at least 4 points were conserved in PKT5 sequence.
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PMID:Sequence analysis of a mitochondrial DNA fragment isolated from cultured cells of carrot cytoplasmic male-sterile strain. 181 76

Alterations in the rat brain carbohydrate and related metabolisms were studied during acute and chronic acephate toxicity. The rats were divided into three batches of eight in each batch. The first batch was treated with chronic (50 mg.Kg-1.day-1 for 7 weeks) and second batch was treated with acute (600 mg.Kg-1.day-1 for one day) doses of acephate, third group was served as control which received vehicle only. The representative enzymes like SDH, MDH, LDH, GDH, AAT and AlAT activities were decreased significantly during chronic treatment. Whereas MDH, LDH, AAT and AlAT activities showed significant increase during acute treatment. The glycogen and pyruvate levels showed nonsignificant elevation and lactate and total carbohydrate levels were depleted in the brains of chronic acephate treated rats. Reverse trend was observed with regard to lactate and pyruvate during acute toxicity whereas the total carbohydrates and glycogen levels were significantly elevated. The decreased oxidative potential and reduced flux of ketoacids into TCA cycle through transamination reactions indicate that acephate caused energy crisis in the brain during chronic treatment. During acute treatment the inhibited succinate oxidation was compensated by the ketoacid contributions through transamination reactions. The neuro transmitter balance with particular reference to glutamate during toxic stress was reflected through the GDH levels in both the treatments.
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PMID:Alterations in glycolytic and oxidative potentials of rat brain during acute and chronic acephate treatments. 195 6


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