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)

The expression of colicin genes is controlled by the SOS-system (Lex A repressor) and the adenylate-cyclase system (cAMP-CAP complex). The effect of plasmid DNA supercoiling on the expression of the operons of colicins E1, E2, and E3 has been studied by using E. coli minicells. It has been shown for the colicin E1 operon that it is the promoter that is influenced by supercoiling: an increase in negative supercoiling elevates the expression and, vice versa, DNA relaxation reduces the expression. The effect of supercoiling on gene activity of the colicin E1 immunity protein has not been observed, which may be due to the specific orientation of this gene. With the two other colicins supercoiling affects the expression of all genes which constitute the operon. The regulation of the colicin operon expression has been confirmed to occur at three levels: by the LexA protein, by the cAMP-CAP complex, and by the plasmid DNA supercoiling.
Mol Biol (Mosk)
PMID:[The effect of supercoiling of DNA from colicinogenic plasmids on the expression of col, imm and lys genes]. 269 78

In medium 199 plus 20% fetal calf serum adult rat cardiomyocytes establish a long-term culture (25 days). During the first 10 days they change their gross morphology from the typical elongated in vivo shape (day 1), to a smooth spherical intermediate form (days 2 to 5), to a spread cell type beating spontaneously (days 10 to 15). During the first 10 days in culture, protein content per cell increases and the cell population decreases. By the tenth day, protein content has doubled, and about half of the cells originally plated remain. Thereafter both the protein content and the number of cells are essentially constant for the remainder of the 25-day period investigated. On days 1, 15 and 25 adenine nucleotide contents (213, 216 and 225 nmol/10(6) cells) and values of adenylate energy charge (0.91, 0.87 and 0.88) were similar. At all times in culture, palmitate (0.1 mM) is oxidized at higher rates than lactate (1 mM) and glucose (5 mM). At all times in culture glycolytic flux is sensitive to insulin with half maximal effect seen around 10(-9) M. Oxidation rates for all exogenous substrates are maximal at 15 days in culture, indicating maximal energy demand at this time. The conversion of glucose to lactate, however, progressively increases, so that at 25 days in culture, 70% of ATP derived from degradation of exogenous glucose is glycolytic. The results of this study demonstrate that oxidative metabolism of cardiomyocytes in long-term culture resembles, in its basic characteristics, that of the intact heart. In their increased glycolytic activity, however, they are clearly different.
J Mol Cell Cardiol 1989 Feb
PMID:Substrate oxidation by adult cardiomyocytes in long-term primary culture. 274 49

Detachment of flagella in Chlamydomonas reinhardii stimulates a rapid accumulation of tubulin mRNAs. The induced tubulin mRNAs are normally rapidly degraded following flagellar regeneration, but inhibition of protein synthesis with cycloheximide prevents their degradation. alpha-Tubulin poly(A) tail lengths were measured during normal accumulation and degradation, and in cycloheximide-treated cells. To measure alpha-tubulin mRNA poly(A) chain lengths with high resolution, specific 3' fragments of alpha 1- and alpha 2-tubulin mRNAs, generated by RNase H digestion of mRNA-oligonucleotide hybrids, were sized by Northern analysis. Both alpha-tubulin mRNAs have a newly synthesized poly(A) chain of about 110 adenylate residues. The poly(A) tails shorten with time, and show an average length of 40 to 60 adenylate residues by 90 minutes after deflagellation, at which time induced alpha-tubulin mRNA is being rapidly degraded. Poly(A) loss is significantly accelerated in cycloheximide-treated cells, and this loss is not attributible simply to the longer time the stabilized molecules spend in the cytoplasm. A large fraction of alpha-tubulin mRNA accumulates as mRNA with very short poly(A) tails (less than 10 residues) in the presence of cycloheximide, indicating that deadenylated alpha-tubulin mRNAs can be stable in vivo, at least in the absence of protein synthesis. The rate and extent of poly(A) loss in cycloheximide are greater for alpha 2-tubulin mRNA than for alpha 1-tubulin mRNA. This difference cannot be attributed to differential ribosome loading. This finding is interesting in that the two mRNAs are very similar in sequence with the exception of their 3' untranslated regions.
J Mol Biol 1989 Jun 20
PMID:Accelerated poly(A) loss on alpha-tubulin mRNAs during protein synthesis inhibition in Chlamydomonas. 276 Sep 30

Adenylate kinase from yeast cytosol was crystallized as a 1:1 complex with the inhibitor P1,P5-di(adenosine-5'-)pentaphosphate. The crystalline structure was solved by multiple isomorphous replacement at a resolution of 3 A (1 A = 0.1 nm) and subsequent structural refinement at 2.6 A resolution. The yeast enzyme belongs to the group of large variants among the adenylate kinases, whereas the structurally known porcine cytosolic enzyme is a small variant. A comparison showed that the additional 31-residue segment of the large variants covers the active center. This had not been expected, because small and large variants show similar enzyme kinetics. Apart from this insertion, the chain folds of both adenylate kinases are the same. The yeast enzyme with bound inhibitor, however, assumes a much more closed form. In relation to the porcine enzyme without substrate, a segment of 28 residues containing two helices is rotated by about 30 degrees, closing the deep cleft at the active center. This corresponds to the expected induced fit. Sequence comparisons with other adenylate kinases suggest that one of the adenosine moieties of the inhibitor does not bind at a native nucleotide-binding site of the enzyme.
J Mol Biol 1987 Jun 05
PMID:Structure of the complex of yeast adenylate kinase with the inhibitor P1,P5-di(adenosine-5'-)pentaphosphate at 2.6 A resolution. 282 Dec 81

1. Substrates for cAMP-dependent protein kinase were investigated in anterior, intermediate, and neural lobes of the rat pituitary gland. In a cell-free assay system, cAMP increased phosphorylation of 17 K, 33 K, and 60 K macromolecules of the anterior lobe, 17 K, 33 K, 60 K, and 80 K macromolecules of the intermediate lobe, and 60 K, 80 K, and 85 K macromolecules of the neural lobe. 2. Other nucleotides were tested in the intermediate lobe; 8 Br-cAMP mimicked cAMP, cGMP was much less effective than cAMP or 8 Br-cAMP, and 5'-AMP showed no significant effect. The purified catalytic subunit of cAMP-dependent protein kinase evoked the same phosphorylation pattern as the endogenous kinase. 3. Maximum cAMP-dependent phosphorylation occurred at between 1 and 2 min of incubation; after 20 min, phosphorylation was reduced by 80%. This suggests the presence of phosphatase activity in the intermediate lobe. 4. When tested upon dispersed intermediate lobe cells permeabilized by high-voltage electrical discharges, cAMP increased phosphorylation of the 17 K and 33 K macromolecules.
Cell Mol Neurobiol 1988 Mar
PMID:Substrates for adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase in the rat pituitary gland. 284 Oct 26

The cellular mechanism of action of the cannabimimetic drugs is examined using cultured cells. In membranes from N18TG2 neuroblastoma cells and the neuroblastoma X glioma hybrid cells, NG108-15, the psychoactive cannabinoid drugs and their nantradol analogs could inhibit adenylate cyclase activity. This response was not observed in either the soluble adenylate cyclase from rat sperm or membrane-bound adenylate cyclases from C6 glioma or S49 lymphoma cells. This cellular selectivity provides further evidence for the existence of specific receptors for the cannabimimetic compounds. Receptor-mediated inhibition of adenylate cyclase requires the presence of a guanine nucleotide-binding protein complex, Gi. Gi can be functionally inactivated as a result of an ADP-ribosylation modification catalyzed by pertussis toxin. The present study demonstrates that pertussis toxin treatment of cells abolished the cannabimimetic response in intact cells and in membranes derived therefrom. The action of pertussis toxin required NAD+ as substrate for in vitro modification of neuroblastoma membranes. Furthermore, pertussis toxin was able to catalyze the labeling of a neuroblastoma membrane protein in vitro using [32P] NAD+ under conditions similar to those by which attenuation of the cannabimimetic inhibition of adenylate cyclase could be demonstrated. This evidence demonstrates the requirement for a functional Gi in the action of cannabimimetic drugs.
Mol Pharmacol 1986 Mar
PMID:Involvement of Gi in the inhibition of adenylate cyclase by cannabimimetic drugs. 286 5

The adenylate cyclase toxin of the prokaryote Bordetella pertussis is stimulated by the eukaryotic regulatory protein, calmodulin. A general strategy, using the adenylate-cyclase-calmodulin interaction as a tool, has permitted cloning and expression of the toxin in Escherichia coli in the absence of any B. pertussis trans-activating factor. We show that the protein is synthesized in a large precursor form composed of 1706 amino acids. The calmodulin-stimulated catalytic activity resides in the amino-terminal 450 amino acids of the adenylate cyclase. The enzyme expressed in E. coli is recognized in Western blots by antibodies directed against purified B. pertussis adenylate cyclase, and its activity is inhibited by these antibodies.
Mol Microbiol 1988 Jan
PMID:The calmodulin-sensitive adenylate cyclase of Bordetella pertussis: cloning and expression in Escherichia coli. 289 67

Octopamine, a major aminergic neurotransmitter in invertebrates, exerts many of its actions through receptors which are associated with the activation of adenylate cyclase. The present study defines and characterizes a new class of potent octopamine agonists, the substituted phenyliminoimidazolidines (PIIs). Approximately 30 of these derivatives were examined for agonist and antagonist effects on the highly enriched and specific octopamine-sensitive adenylate cyclase present in the firefly light organ, as well as on adenylate cyclases present in other invertebrate and vertebrate tissues. Several derivatives were extremely active and some (e.g. 2,6-diethyl-PII) had potencies exceeding those of any previously described agonists of octopamine-sensitive adenylate cyclase. Stimulation by the potent PIIs was reversible, nonadditive to that caused by octopamine, and could be antagonized by antagonists such as cyproheptadine (Ki = 4 microM), phentolamine (Ki = 23 microM), and propranolol (Ki = 72 microM). These inhibitory constants agreed well with those for inhibiting octopamine stimulation. Certain PII derivatives acted as partial agonists and some as antagonists of octopamine stimulation. Structure-activity relationships revealed, among other things, that short-chain alkyl substitution in the 2- and 6-phenyl positions enhanced activity, as did further substitution of 4-halo, 4-methyl, or 4-hydroxy substituents. 4-Amino or N-alkyl substitution decreased activity. Structurally related benzylimidazoline derivatives such as tolazoline and naphazoline were partial octopamine agonists, generally less active than the PIIs. Comparison, in three invertebrate species, of the effects of the PIIs and two other chemical classes of octopamine agonists demonstrated clearcut differences in species responsiveness. Other comparative studies revealed that the agonist activity of the potent PIIs was specific for tissues containing an octopamine-sensitive adenylate cyclase; adenylate cyclases activated by dopamine or by beta 1- or beta 2-adrenergic agonists were unaffected by these compounds. Evaluation of the relative binding affinities of various PIIs for mammalian alpha-adrenergic receptors, as well as the ability of various antagonists to block PII binding, strongly suggested that the active PIIs are affecting a class of octopamine receptors distinct from mammalian alpha 1- or alpha 2-adrenergic receptors. These octopamine receptors also appeared distinct from mammalian 5-HT1 and 5-HT2 receptors. Correlative physiological studies in insects revealed that the active PIIs mimicked octopamine and were potent activators of light emission in the firefly light organ.(ABSTRACT TRUNCATED AT 400 WORDS)
Mol Pharmacol 1985 Sep
PMID:Phenyliminoimidazolidines. Characterization of a class of potent agonists of octopamine-sensitive adenylate cyclase and their use in understanding the pharmacology of octopamine receptors. 299 48

We have examined adenylate cyclase (AC) in the M2R melanoma cell line, a novel clone of transplantable B16 melanoma cells. It has been found that activity of this enzyme is highly responsive to beta-melanotropin (beta-MSH) and other hormones possessing melanotropic activity (e.g., alpha-melanotropin (alpha-MSH) and adrenocorticotrophic hormone (ACTH1-24)). beta-MSH stimulation of adenylate cyclase, both in the intact cell and in a plasma membrane-enriched fraction derived thereof, was shown to be saturable and dose-dependent. In addition, prostaglandin E1 (PGE1) was found to be a potent stimulator of AC activity in these cells. Hormone stimulation of enzyme activity in the intact cell was strongly potentiated by forskolin which not only enhanced maximal AC activity 3-fold, but lowered by 40-fold the concentration of beta-MSH required for half-maximal stimulation. Using biologically active [125I]iodo-beta-MSH prepared in our laboratory we have examined the specificity of beta-MSH binding to its receptor in both intact M2R cells and plasma membranes derived thereof. Among a series of hormones tested only alpha-MSH and ACTH1-24 competed with [125I]iodo-beta-MSH for binding to the melanotropin receptor in accordance with the results obtained with AC. In contrast to the strong effect on cyclic 3',5'-adenosine monophosphate (cAMP) accumulation in M2R cells forskolin has no effect on [125I]iodo-beta-MSH binding. It appears that the kinetic properties of beta-MSH binding and beta-MSH stimulation of adenylate cyclase activity are essentially identical, the half-maximal effects of which are demonstrated at approximately 20 nM beta-MSH.
Mol Cell Endocrinol 1986 Jul
PMID:Regulation of adenylate cyclase by beta-melanotropin in the M2R melanoma cell line. 301 5

Single crystals of an amino-terminal fragment of Escherichia coli alanine tRNA synthetase have been prepared by the vapor diffusion method. The fragment extends to amino acid residue 368 and catalyzes the synthesis of alanyl adenylate. The crystals grow in the presence of alanine as rhombic plates in space group P2(1)2(1)2(1) and with unit cell dimensions of a = 67.9 A, b = 98.5 A and c = 123.6 A (1 A = 0.1 nm). They diffract to better than 3 A resolution.
J Mol Biol 1988 Sep 20
PMID:Crystallization of a small fragment of an aminoacyl tRNA synthetase. 305 89


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