Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ADENINE”

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 703 records · Page 39Linked to original sources
PubMed1990

Sequence specific conformation of a DNA decamer containing an adenine tract studied in solution by H-NMR spectroscopy.

The decanucleotide duplex d(AAAACGTTTT)2 and a variety of phase-sensitive two-dimensional (2D) NMR experiments have been used to investigate the solution conformation of an adenine-tract and its junction with another DNA sequence. 2D nuclear Overhauser effect data confirm that the oligonucleotide has a general B-type DNA morphology but an array of unusual correlations implies that the adenine tract and the 5'-ApC junction have conformations more compatible with the modified X-ray structures recently reported for DNAs of similar sequence (Nelson, H.C.M., Finch, J.T., Luisi, B.F. and Klug, A. (1987) Nature 330, 221-226). The pattern and magnitude of interstrand NOEs from the adenine H2s to the sugar H1's of the complementary base to the 5'-neighbouring residue indicate that the A-T basepairs are highly propeller twisted and that the minor groove is narrowed, showing its greatest compression at the 3'-end of the tract at the 5'-ApC step. Quantifying spin-coupling interactions within the deoxyribose rings by analysing both 1D and high-resolution 2D DQF-COSY data reveals that the conformation of the purines is predominantly C2'-endo, with the pseudorotation phase angle P lying in the range 140-180 degrees. For the pyrimidines, however, there are distortions away from this standard B-type geometry with the data being best described by P values lying in the range 90-130 degrees (i.e., O4'-endo, C1'-exo). The sugar puckers of A1, T9 and T10 are dynamically distorted no doubt as a consequence of their positions at, or close to, the ends of the duplex. Thus the conformation of the adenine and thymine sugars within the oligo(dA) and oligo(dT) strands are different with an abrupt change in sugar puckering occurring at the 5'-ApC (5'-GpT) step. Peculiar chemical shifts values for A4H2, T7CH3 and sugar C5 H1', H2' and H2", together with a number of interresidue NOEs with unusual intensities, imply that there are also substantial modifications to basepair stacking interactions at this step. Taken as a whole, our data are consistent with the view that the conformational dislocation at the 5'-ApC dinucleotide results from a combination of slide and roll manoeuvres and that the junction between the AAAA and CG sequences is a potential nucleation site for DNA bending.

Adenine↗
PubMed1988

Substrate sites of the (Na+ + K+)-ATPase: pertinence of the adenine and fluorescein binding sites.

The (Na+ + K+)-activated ATPase catalyzes the K+-activated hydrolysis of 3-O-methylfluorescein phosphate (3OMFP) with a Km of 50 microM, nearly two orders of magnitude lower than the Km for nitrophenyl phosphate, 3 mM. Both ATP and nitrophenyl phosphate are competitors toward 3OMFP with Ki values corresponding to their Km values (for ATP that at the low-affinity sites of the E2 conformation). Enzyme treated with fluorescein isothiocyanate (FITC) such that 60% of the (Na+ + K+)-ATPase activity is lost still hydrolyzes both 3OMFP and nitrophenyl phosphate: the apparent Km values are increased less than 2-fold and the Vmax is unaffected. ATP still inhibits these K+-phosphatase reactions of the FITC-treated enzyme, and this inhibition can exceed the 40% of residual (Na+ + K+)-ATPase activity. Evaluation of a kinetic model indicates that the Ki for ATP is increased about an order of magnitude by FITC-binding. Similar results obtain with trinitrophenyl-ATP (TNP-ATP) as inhibitor, in this case with Ki values in the micromolar range. Finally, FITC treatment increases K+-activated ADPase activity. These observations are interpreted as the fluorescein ring of 3OMFP binding to the adenine pocket of the substrate site, thereby conferring high affinity, just as the fluorescein ring of FITC binding to the adenine pocket in the E1 conformation permits specific linkage of the isothiocyanate chain to a particular lysine, Lys-501. Then, coincident with the transition to the E2 conformation, which bears the low-affinity site for ATP and which catalyzes the K+-phosphatase reaction, the FITC molecule tethered to Lys-501 is pulled from the adenine pocket: allowing 3OMFP and ADP to bind as substrates and ATP and TNP-ATP as inhibitors, albeit in altered conformation. The E1 to E2 transition thus involves not only a change from high to low affinity for ATP, but also a distortion of the adenine pocket and the orientation between Lys-501 and Asp-369, the residue associated with catalysis.

Adenine↗
PubMed1989

Characterization of adenine phosphoribosyltransferase from the human malaria parasite, Plasmodium falciparum.

Because of their inability to synthesize purines de novo, malaria parasites rely on purine phosphoribosyltransferases (PRTases) to convert purine bases salvaged from the host cell (the erythrocyte) into the corresponding purine nucleoside monophosphates. Our studies with late trophozoites of the human malaria parasite, Plasmodium falciparum, showed that virtually all of the purine PRTase activity is accounted for by two distinct enzymes. One enzyme utilizes hypoxanthine, guanine and xanthine (Queen, S.A., Vander Jagt, D. and Reyes, P. (1988) Mol. Biochem. Parasitol. 30, 123-134). The second enzyme utilizes only adenine and is the subject of this paper. This latter enzyme exhibits a biphasic pH-activity profile and is moderately to weakly inhibited by several divalent metal ions. Several of the properties of the P. falciparum enzyme were found to differ significantly from those of human erythrocyte adenine PRTase. (1) The molecular weight (18,000) of the parasite enzyme is smaller than that of the host cell enzyme. (2) The parasite enzyme, unlike the erythrocyte enzyme, is not significantly inhibited by sulfhydryl reagents. (3) 6-Mercaptopurine and 2,6-diaminopurine proved to be competitive inhibitors of the parasite enzyme (Ki 0.70 and 1.0 mM, respectively); on the other hand, the human enzyme is not inhibited by these agents. (4) The Km for adenine (0.80 microM) and 5-phosphoribosyl-1-pyrophosphate (0.70 microM) displayed by the parasite enzyme are significantly smaller than the corresponding Km values shown by the erythrocyte enzyme. These distinctions between the parasite and host enzymes point to the possibility that adenine PRTase of P. falciparum may represent a potential target for chemotherapeutic attack.

Adenine Phosphoribosyltransferase↗
PubMed1976

Studies on adenine and adenosine metabolism by intact human erythrocytes using high performance liquid chromatography.

Adenine and adenosine metabolism has been studied in intact human erythrocytes in vitro using high performance liquid chromatography, isotopic labeling and electrophoresis. Their metabolism to nucleotides was controlled by phosphoribose diphosphate synthesis which was phosphate dependent. Adenosine formed hypoxanthine or IMP depending upon Pi concentration, but adenosine kinase and deaminase activities were not affected by P levels. Free [14C]adenine and [14C]hypoxanthine were found in cellular extracts. Rapid interconversions occurred to give a distribution for ATP : ADP : AMP of 10 : 1 : 0.1. Marked decomposition of ATP to ADP and AMP occurred during incubations in plasma and Earle's media in air on nitrogen, but ATP levels remained stable in phosphate buffers and in the presence of oxygen. At physiological Pi (1 mM) adenosine kinase activity grossly exceeded adenine phosphoribosyltransferase activity. The latter was approximately 7 fold that of hypoxanthine phosphoribosyltransferase activity. These differences decreased with increasing Pi levels. No significant increase in corresponding nucleotides was obtained by incubation with high levels (0.5 mM) of adenine, guanine or guanosine at physiological Ii, ATP increased by 10% independently of the substrate employed and significant amounts of IMP and GTP were formed adenosine and guanosine, respectively. The existence of a bound intracellular pool of ATP is suggested.

Adenine↗
PubMed1983

Adenine-induced hypoxanthine release from IMP-enriched human erythrocytes.

Adenine uptake and hypoxanthine release by IMP-enriched human erythrocytes has been studied. The presence of IMP within the erythrocytes leads to an increase in the rate of adenine incorporation. Adenine is taken up by IMP-enriched erythrocytes as AMP, even when intracellular 5-phosphoribosyl-1-pyrophosphate concentration is undetectable and too low to allow IMP synthesis from hypoxanthine. During adenine uptake and AMP synthesis, hypoxanthine is released by the cells. The possibility that 5-phosphoribosyl-1-pyrophosphate, necessary for AMP synthesis, is formed through the hypoxanthine guanine phosphoribosyltransferase-catalyzed IMP pyrophosphorolysis is considered.

Adenine↗
PubMed1984

Crystal structure of 3-(adenin-9-yl)propionhistamide hydrochloride monohydrate and the role of protonation in protein-nucleic acid interactions.

The three-dimensional structure of 3-(adenin-9-yl)propionhistamide hydrochloride, as a model of interactions between the protonated imidazolyl group and adenine moiety, has been determined by X-ray crystallography. The crystal data are a = 10.314 (1), b = 7.854 (1), c = 20.780 (1) A, beta = 92.765 (4), Z = 4, Dm = 1.32 g X cm-3, space group P2(1)/n. The imidazolium group interacts with adenine moiety by stacking. A comparison with the related neutral derivatives leads to a hypothesis that adenine stacks with the protonated, but not with the neutral, imidazolyl group. Such a characteristic behaviour of the imidazolyl group depending on protonation was shown by ultraviolet and NMR spectroscopy, and by polarographic experiments in solution. We note that a role of the essential histidine in RNAase reaction is a switch between capture and ejection of the substrate, which depends upon proton uptake and its release, respectively.

Adenine↗
PubMed1984

Regulation of hepatic gluconeogenesis by rapid compartmentation of mitochondrial adenine nucleotides in the newborn rabbit.

In newborn rabbit liver the mitochondrial adenine nucleotide pool (ATP + ADP + AMP) size increased from 6.4 +/- 0.4 to 14.5 +/- 0.7 nmol/mg mitochondrial protein within 2 hr after birth. Gluconeogenesis (from lactate) in isolated hepatocytes rose from 13.1 +/- 1.9 at birth to 42.3 +/- 2.4 nmol glucose/min/10(7) cells at 2 hr. Pyruvate carboxylation in isolated mitochondria increased in parallel from 42.8 +/- 4.9 at birth to 108.6 +/- 8.2 nmol H14CO-3/min/mg mitochondrial protein at 2 hr. The similar developmental time course for these three phenomena suggested that the rapid increase in gluconeogenesis might be a result of increased availability of adenine nucleotides to the ATP-requiring mitochondrial enzyme, pyruvate carboxylase. Manipulation of the mitochondrial adenine nucleotide pool size in vitro resulted in predictable changes in the rate of pyruvate carboxylation. We concluded that the postnatal increase in mitochondrial adenine nucleotide content stimulates pyruvate carboxylation, thereby causing a rapid increase in the rate of gluconeogenesis.

Adenine Nucleotides↗
PubMed1985

Adenine nucleotide metabolism in pigeon liver and heart: diurnal changes and correlations between indices.

The adenine nucleotide and Pi content of pigeon liver and heart were determined, and the energy charge, phosphoryl potential and mass action ratio of adenylate kinase were calculated over the 24 hr period. All the indices of adenine nucleotide metabolism were shown to vary a 2- to 4-fold extent, both in liver and heart. The correlation coefficients for each of the adenine nucleotides and each of the calculated indices were computed and shown to be different for liver and heart. The difference between pigeon liver, pigeon heart and rat liver in the diurnal variation of adenine nucleotide metabolism, in the regulatory mechanism, and in metabolism on the whole is discussed.

Adenine Nucleotides↗
PubMedDate not supplied

Do adenine derivatives have a special role in biological regulation?

The hypothesis is raised "that adenine by way of its many derivatives plays an important role in regulating a wide variety of biological functions". Evidence is cited for such a role in cell-to-cell communication, intracellular regulation and interorganism communication. It is predicted that many more key biological functions will be found to be modulated by adenine derivatives and that adenine compounds which have not yet been studied in great depth will become recognized as biological regulators. The hypothesis also predicts that some disease states may be caused by perturbations of the adenine derivative-receptor system.

Adenine Nucleotides↗
PubMed1995

Inhibition of hydroxyl radical production by lactobionate, adenine, and tempol.

Superoxide and hydroxyl free radicals are strongly implicated in the deleterious effects of reperfusion of grafted organs. Iron ions are critical in the Fenton-like reaction that generates oxygen-free radicals from H2O2. Using the ADP/Fe2+/H2O2 .OH-generating system, we demonstrated that components of an organ-preservation solution (Henri Mondor solution): sodium lactobionate, adenine, and a nitroxide radical: 4-hydroxy-2,2,6,6-tetramethylpiperidine-n-oxyl (TEMPOL), showed unexpected inhibition properties on the production of hydroxyl radicals by complexation of Fe2+ for lactobionate and nitroxide or Fe3+ for adenine. This inhibition was 75.5% at 12 mM lactobionate. Moreover, a complete inhibition was observed at 50 mM. At 0.25 mM adenine, the reduction was 14.8% (maximum effect: 34.1%). Henri Mondor solution, at an identical adenine and lactobionate concentration, inhibited the radical production by 91.5%, indicating an additive effect. Nitroxide totally inhibited .OH production by the ADP/Fe2+/H2O2 system (maximum effect: 95.6%) and partially the production by an O2.- generating system (maximum effect: 74.8%). Thus, the association of these three components in preservation solutions would be an original method to limit the reperfusion injury observed in isolated ischemic organs.

Adenine↗
PubMed2005

Consecutive adenine sequences are potential targets in photosensitized DNA damage.

Based on direct spectroscopic measurements of hole transfer in DNA and quantification of the yield of DNA oxidative damage, consecutive adenine sequences were found to be a good launching site for photosensitizers to inject a hole in DNA, where the following rapid hole transfer between adenines causes a long-lived charge-separated state leading to DNA oxidative damage. According to the results, the essential requisites for an efficient and/or harmful photosensitizer are determined as follows: to be able to oxidize adenine to trigger hole transfer between adenines, and react rapidly with molecular oxygen following its reduction, avoiding charge recombination and making the reaction irreversible. These results will greatly help us to classify photosensitizers harmful to human health, and to design an improved photosensitizer for biochemical applications.

Adenine↗
PubMed2006

Folding of the adenine riboswitch.

The pbuE adenine riboswitch undergoes metal ion-dependent folding that involves a loop-loop interaction. Binding of 2-aminopurine to the aptamer domain strongly correlates with the ability of the loops to interact, and single-molecule FRET studies reveal that folding proceeds via a discrete intermediate. Folding occurs in the absence of adenine ligand, but ligand binding stabilizes the folded structure by increasing the folding rate and decreasing the unfolding rate, and it lowers the magnesium ion concentration required to promote the loop-loop interaction. Individual aptamer molecules exhibit great heterogeneity in folding and unfolding rates, but this is reduced in the presence of adenine. In the full riboswitch, the adenine binding domain fails to fold because of conformational competition by the terminator stem. Thus, riboswitch function should depend on the relative rates of ligand binding and the transcriptional process.

2-Aminopurine↗
PubMed2006

Flow injection determination of adenine at trace level based on luminol-K2Cr2O7 chemiluminescence in a micellar medium.

A novel flow injection chemiluminescence (CL) analysis method for the determination of adenine in the presence of sodium dodecylbenzene sulfonate (SDBS) surfactant micelles is described. This method is based on the luminescent properties of the luminol-K2Cr2O7-adenine in alkaline medium sensitized by SDBS. The optimized experimental conditions were evaluated and the possible mechanism was discussed by examining CL emission spectrum and the effect of various free radical scavengers on CL emission intensity. The CL increase is linearly related to the concentration of adenine in the range of 2.92x10(-6) to 4.38x10(-10) mol l-1 with a detection limit of 2.46x10(-10) mol l-1 (S/N=3). The relative standard deviation for 2.92x10(-7) mol l-1 samples was 1.67% (n=12). The proposed method has been applied to the determination of adenine in human serum.

Adenine↗
PubMed2005

KATP channel interaction with adenine nucleotides.

ATP-sensitive potassium (K(ATP)) channels are regulated by adenine nucleotides to convert changes in cellular metabolic levels into membrane excitability. Hence, elucidation of interaction of SUR and Kir6.x with adenine nucleotides is an important issue to understand the molecular mechanisms underlying the metabolic regulation of the K(ATP) channels. We analyzed direct interactions with adenine nucleotides of each subunit of K(ATP) channels. Kir6.2 binds adenine nucleotides in a Mg(2+)-independent manner. SUR has two NBFs which are not equivalent: NBF1 is a Mg(2+)-independent high affinity nucleotide binding site, whereas NBF2 is a Mg-dependent low affinity site. Although SUR has ATPase activity at NBF2, it is not used to transport substrates against the concentration gradient unlike other ABC proteins. The ATPase cycle at NBF2 serves as a sensor of cellular metabolism. This may explain the low ATP hydrolysis rate compared to other ABC proteins. Based on studies of photoaffinity labeling, a model of K(ATP) channel regulation is proposed, in which K(ATP) channel activity is regulated by SUR via monitoring the intracellular MgADP concentration. K(ATP) channel activation is expected to be induced by the cooperative interaction of ATP binding at NBF1 and MgADP binding at NBF2.

Adenine↗
PubMed1988

Homology of histone H1 variants with adenine nucleotide-binding proteins.

Significant homology was observed between the adenine nucleotide-binding domain in the catalytic subunit of bovine protein kinase A and the carboxy-terminal half of the globular domain of histone H1. A consensus sequence deducible from several previously characterized adenine nucleotide-binding sites is totally conserved in H1. In addition, several putative phosphate binding-sites were observed within the carboxyterminal tail and one in the cluster of basic amino acids in the aminoterminal tail. Both the putative adenine and phosphate-binding sites are well conserved through evolution in various species and in different H1 variants. The present data thus suggest that histone H1 variants may bind to adenine derivatives and imply that they may recognize a specific nucleotide sequence in DNA.

Adenine Nucleotides↗
PubMed2003

Determination of pyridine and adenine nucleotide metabolites in Bacillus subtilis cell extract by sweeping borate complexation capillary electrophoresis.

With a growing interest in new areas of bioanalytical research such as metabolome analysis, the development of sensitive capillary electrophoresis (CE) methods to analyze sub-microM concentrations of analytes in biological samples is required. In this report, the application of CE with sweeping by borate complexation is used to analyze a group of seven pyridine and adenine nucleotide metabolites derived from bacteria Bacillus subtilis cell extracts. Nanomolar (nM) detectability of analytes by CE with UV photometric detection is achieved through effective focusing of large sample plug (approximately 10% of capillary length) using sweeping by borate complexation method, reflected by a limit of detections (S/N = 3) of about 2 x 10(-8) M. Changes in metabolites concentrations were observed in cell extracts when using either glucose or malate as the carbon source in the culture medium. Concentration of pyridine and adenine nucleotides in cell extracts varied widely from 78.6 (+/-7.6) microM for nicotinamide-adenine dinucleotide in malate to 0.66 (+/-0.12) microM for nicotinamide-adenine dinucleotide phosphate in glucose culture medium. Concentrations of metabolites in a single cell were also estimated at millimolar (mM) level. The method was validated in terms of linearity, sensitivity and reproducibility. The application of CE by sweeping borate complexation allows for sensitive and reproducible analyses of nucleotide metabolites in complex biological samples such as bacteria cell extracts.

Adenine Nucleotides↗
PubMed2003

Insight into the functional consequences of inherited variants of the hMYH adenine glycosylase associated with colorectal cancer: complementation assays with hMYH variants and pre-steady-state kinetics of the corresponding mutated E.coli enzymes.

The oxidized guanine lesion 7,8-dihydro-8-oxo-2'-deoxyguanosine (OG) is highly mutagenic, resulting in G:C to T:A transversion mutations in the absence of repair. The Escherichia coli adenine glycosylase MutY and its human homolog (hMYH) play an important role in the prevention of mutations associated with OG by removing misincorporated adenine residues from OG:A mismatches. Previously, biallelic mutations of hMYH have been identified in a British family (Family N) with symptoms characteristic of familial adenomatous polyposis (FAP), which is typically associated with mutations in the adenomatous polyposis coli (APC) gene. Afflicted members of this family were compound heterozygotes for two mutations in hMYH, Y165C and G382D. These positions are highly conserved in MutY across phylogeny. The current work reveals a reduced ability of the hMYH variants compared to wild-type (WT) hMYH to complement the activity of E.coli MutY in mutY((-)) E.coli. In vitro analysis of the corresponding mutations in E.coli MutY revealed a reduction in the adenine glycosylase activity of the enzymes. In addition, evaluation of substrate affinity using a substrate analog, 2'-deoxy-2'-fluoroadenosine (FA) revealed that both mutations severely diminish the ability to recognize FA, and discriminate between OG and G. Importantly, adenine removal with both the mutant and WT E.coli enzymes was observed to be less efficient from a mismatch in the sequence context observed to be predominantly mutated in tumors of Family N. Interestingly, the magnitude of the reduced activity of the E.coli mutant enzymes relative to the WT enzyme was magnified in the "hotspot" sequence context. If the corresponding mutations in hMYH cause similar sensitivity to sequence context, this effect may contribute to the specific targeting of the APC gene. The lack of complementation of the hMYH variants for MutY, and the reduced activity of the Y82C and G253D E.coli enzymes, provide additional circumstantial evidence that the somatic mutations in APC, and the occurrence of FAP in Family N, are due to a reduced ability of the Y165C and G382D hMYH enzymes to recognize and repair OG:A mismatches.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2006

DamID: mapping of in vivo protein-genome interactions using tethered DNA adenine methyltransferase.

A large variety of proteins bind to specific parts of the genome to regulate gene expression, DNA replication, and chromatin structure. DamID is a powerful method used to map the genomic interaction sites of these proteins in vivo. It is based on fusing a protein of interest to Escherichia coli DNA adenine methyltransferase (dam). Expression of this fusion protein in vivo leads to preferential methylation of adenines in DNA surrounding the native binding sites of the dam fusion partner. Because adenine methylation does not occur endogenously in most eukaryotes, it provides a unique tag to mark protein interaction sites. The adenine-methylated DNA fragments are isolated by selective polymerase chain reaction amplification and can be identified by microarray hybridization. We and others have successfully applied DamID to the genome-wide identification of interaction sites of several transcription factors and other chromatin-associated proteins. This chapter discusses DamID technology in detail, and a step-by-step experimental protocol is provided for use in Drosophila cell lines.

Animals↗