Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activities of TdR kinase2 (ATP: thymidine 5'-phosphotransferase, EC 2.7.1.21), AdR kinase (ATP: deoxyadenosine 5'-phosphotransferase, EC 2.7.1.76), GdR kinase (ATP: deoxyguanosine 5'-phosphotransferase, without EC number), ATP (Mg2+)-ase (ATP phosphohydrolase, EC 3.6.1.3), nucleoside diphosphatase (nucleoside diphosphate phosphohydrolase, EC 3.6.1.6), nucleoside phosphotransferase (AMP: deoxynucleoside phosphotransferase, EC 2.7.1.77) and ribonucleotide 5'-diphosphate reductase (EC 1.17.4.1) were assayed in mitochondria of normal and regenerating rat liver. The activities of deoxynucleoside kinases are regulated: (a) by feedback inhibition of TdR kinase with dTTP and dCTP, and GdR kinase with dGTP; (b) GdR and AdR kinases by AdR and GdR inhibition, respectively; (c) by stimulation of GdR kinase with dTDP, dTTP and dATP. The stimulatory effects are correlated with changes of ATP (Mg2+)-ase and NDP-ase activities in regenerating liver mitochondria.
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PMID:Regulation of deoxynucleoside kinase activities in rat liver mitochondria. 612 3

cis-Malonato-diammino platinum(II) significantly inhibited P-388 lymphocytic leukemia cell proliferation at 10 mg/kg/day. Incorporation studies showed that DNA synthesis was inhibited following in vivo drug therapy. The major inhibitory effects appeared to be on thymidine kinase and dihydrofolate reductase activities and on overall purine synthesis, with marginal effects on DNA polymerase and ribonucleotide reductase activities. In addition to the DNA inhibition, a marked increase in cyclic adenosine 3',5'-monophosphate levels was noted, which correlated with a rapid decrease in histone phosphorylation. Other minor effects of the drug included significant reduction of proteolytic activity, suppression of States 4 and 3 respiration, and an increase in adenosine triphosphatase and acid phosphatase activities of P-388 cells.
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PMID:Effects of cis-malonato-diammino platinum (II) on P-388 lymphocytic leukemia cell metabolism. 742 Feb 82

Analysis of 76 kb of newly sequenced DNA, located between map positions 182 and 258 kb in the 330-kb chlorella virus PBCV-1 genome, revealed 175 open reading frames (ORFs) of 65 codons or longer. One hundred and five of these 175 ORFs were considered major ORFs. Twenty-one of the 105 major ORFs resembled proteins in databases including ribonucleotide reductase small subunit, RNase III, thioredoxin, glutaredoxin, protein disulfide isomerase, deoxynucleoside kinase, frog virus 3 ATPase, Acetobacter cellulose synthase, a bacteriophage encoded endonuclease, and two C-5 cytosine DNA methyltransferases. One of the ORFs was the PBCV-1 major capsid protein. The 105 major ORFs were evenly distributed along the genome. One set of ORFs was separated by 543 nucleotides whereas 75 of the ORFs were separated by fewer than 100 nucleotides. Nineteen of the 175 ORFs resembled other PBCV-1 ORFs, suggesting that they represent either gene duplications or gene families.
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PMID:Analysis of 76 kb of the chlorella virus PBCV-1 330-kb genome: map positions 182 to 258. 880 66

To investigate the kinetic parameters of the crossbridge cycle that regulate force and shortening in cardiac muscle, we compared the mechanical properties of cardiac trabeculae with either ATP or 2-deoxy-ATP (dATP) as the substrate for contraction. Comparisons were made in trabeculae from untreated rats (predominantly V1 myosin) and those treated with propylthiouracil (PTU; V3 myosin). Steady-state hydrolytic activity of cardiac heavy meromyosin (HMM) showed that PTU treatment resulted in >40% reduction of ATPase activity. dATPase activity was >50% elevated above ATPase activity in HMM from both untreated and PTU-treated rats. V(max) of actin-activated hydrolytic activity was also >50% greater with dATP, whereas the K(m) for dATP was similar to that for ATP. This indicates that dATP increased the rate of crossbridge cycling in cardiac muscle. Increases in hydrolytic activity were paralleled by increases of 30% to 80% in isometric force (F(max)), rate of tension redevelopment (k(tr)), and unloaded shortening velocity (V(u)) in trabeculae from both untreated and PTU-treated rats (at maximal Ca(2+) activation), and F-actin sliding speed in an in vitro motility assay (V(f)). These results contrast with the effect of dATP in rabbit psoas and soleus fibers, where F(max) is unchanged even though k(tr), V(u), and V(f) are increased. The substantial enhancement of mechanical performance with dATP in cardiac muscle suggests that it may be a better substrate for contractility than ATP and warrants exploration of ribonucleotide reductase as a target for therapy in heart failure.
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PMID:2-deoxy-ATP enhances contractility of rat cardiac muscle. 1086 10

Amino acids at conserved sites in the residue sequence of 10 ancient proteins, from 844 phylogenetically diverse sources, were used to specify their time of origin in the interval before species divergence from the last common ancestor (LCA). The order of amino acid addition to the genetic code, based on biosynthesis path length and other molecular evidence, provided a reference for evaluating the 'code age' of each residue profile examined. Significantly earlier estimates were obtained for conserved amino acid residues in these proteins than non-conserved residues. Evidence from the primary structure of 'fossil' proteins thus corroborated the biosynthetic order of amino acid addition to the code.Low potential ferredoxin (Fdxn) had the earliest residue profile among the proteins in this study. A phylogenetic tree for 82 prokaryote Fdxn sequences was rooted midway between bacteria and archaea branches. LCA Fdxn had a 23-residue antecedent whose residue profile matched mid-expansion phase codon assignments and included an amide residue. It contained a highly acidic N-terminal region and a non-charged C-terminal region, with all four cysteine residues. This small protein apparently anchored a [4Fe-4S] cluster, ligated by C-terminal cysteines, to a positively charged mineral surface, consistent with mediating e(-) transfer in a primordial surface system before cells appeared. Its negatively charged N-terminal 'attachment site' was highly mutable during evolution of ancestral Fdxn for Bacteria and Archaea, consistent with a loss of function after cell formation. An initial glutamate to lysine substitution may link 'attachment site' removal to early post-expansion phase entry of basic amino acids to the code. As proteins evidently anchored non-charged amide residues initially, surface attachment of cofactors and other functional groups emerges as a general function of pre-cell proteins.A phylogenetic tree of 107 proteolipid (PL) helix-1 sequences from H(+)-ATPase of bacteria, archaea and eukaryotes had its root between prokaryote branches. LCA PL h1 residue profile optimally fit a late expansion phase codon array. Sequence repeats in transmembrane PL helices h1 and h2 indicated formation of the archetypal PL hairpin structure involved successive tandem duplications, initiated within the gene for an 11-residue (or 4-residue) hydrophobic peptide. Ancestral PL h1 lacked acidic residues, in a fundamental departure from the prototype pre-cell protein. By this stage, proteins with a hydrophobic domain had evolved. Its non-polar, late expansion phase residue profile point to ancestral PL being a component of an early permeable cell membrane. Other indicators of cell formation about this stage of code evolution include phospholipid biosynthesis path length, FtsZ residue profile, and late entry of basic amino acids into the genetic code. Estimates based on conserved residues in prokaryote cell septation protein, FtsZ, and proteins involved with synthesis, transcription and replication of DNA revealed FtsZ, ribonucleotide reductase, RNA polymerase core subunits and 5'-->3' flap exonuclease, FEN-1, originated soon after cells putatively evolved. While reverse transcriptase and topoisomerase I, Topo I, appeared late in the pre-divergence era, when the genetic code was essentially complete. The transition from RNA genes to a DNA genome seemingly proceeded via formation of a DNA-RNA heteroduplex. These results suggest formation of DNA awaited evolution of a catalyst with a hydrophobic domain, capable of sequestering radical bearing intermediates in its synthesis from ribonucleotide precursors. Late formation of topology altering protein, Topo I, further suggests consolidation of genes into chromosomes followed synthesis of comparatively thermostable DNA strands.
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PMID:Molecular evolution before the origin of species. 1222 77

A genome-wide transcription profiling of Arabidopsis upon genotoxic stress has been performed using a high-density colony array (HDCA). The array was based on a library of 27 000 cDNA clones derived from Arabidopsis cells challenged with bleomycin plus mitomycin C. The array covers more than 10 000 individual genes (corresponding to at least 40% of Arabidopsis genes). After hybridisation of the HDCA with labelled cDNA probes obtained from genotoxin-treated (bleomycin plus mitomycin C, 6 h) and untreated seedlings, 39 genes revealed an increased and 24 genes a decreased expression among the 3200 highly expressed clones (representing approximately 1200 individual genes because of redundancy of the cDNA library). Of the 4900 clones with a low transcriptional level, the expression of 500 clones was found to be altered and 57 genes with increased and 22 genes with decreased expression were identified by sequence analysis of 135 identified clones. The HDCA results were validated by real-time PCR analysis. For about 80% of genes (34 out of 42), alteration in expression was confirmed, indicating the reliability of the HDCA for transcription profiling. DNA damage and stress-responsive genes encoding, for instance transcription factors (myb protein and WRKY1), the ribonucleotide reductase small subunit (RNR2), thymidine kinase (TK), an AAA-type ATPase, the small subunit of a DNA polymerase and a calmodulin-like protein were found to be strongly upregulated. Also, several genes involved in cell cycle regulation revealed significant alteration in transcription, as detected by real-time PCR analysis, suggesting disturbance of cell cycle progression by mutagen treatment.
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PMID:The transcriptional response of Arabidopsis to genotoxic stress - a high-density colony array study (HDCA). 1296 30

Ostreid herpesvirus 1 (OsHV-1) is the only member of the Herpesviridae that has an invertebrate host and is associated with sporadic mortality in the Pacific oyster (Crassostrea gigas) and other bivalve species. Cryo-electron microscopy of purified capsids revealed the distinctive T=16 icosahedral structure characteristic of herpesviruses, although the preparations examined lacked pentons. The gross genome organization of OsHV-1 was similar to that of certain mammalian herpesviruses (including herpes simplex virus and human cytomegalovirus), consisting of two invertible unique regions (U(L), 167.8 kbp; U(S), 3.4 kbp) each flanked by inverted repeats (TR(L)/IR(L), 7.6 kbp; TR(S)/IR(S), 9.8 kbp), with an additional unique sequence (X, 1.5 kbp) between IR(L) and IR(S). Of the 124 unique genes predicted from the 207 439 bp genome sequence, 38 were members of 12 families of related genes and encoded products related to helicases, inhibitors of apoptosis, deoxyuridine triphosphatase and RING-finger proteins, in addition to membrane-associated proteins. Eight genes in three of the families appeared to be fragmented. Other genes that did not belong to the families were predicted to encode DNA polymerase, the two subunits of ribonucleotide reductase, a helicase, a primase, the ATPase subunit of terminase, a RecB-like protein, additional RING-like proteins, an ion channel and several other membrane-associated proteins. Sequence comparisons showed that OsHV-1 is at best tenuously related to the two classes of vertebrate herpesviruses (those associated with mammals, birds and reptiles, and those associated with bony fish and amphibians). OsHV-1 thus represents a third major class of the herpesviruses.
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PMID:A novel class of herpesvirus with bivalve hosts. 1560 30

We present evidence for a complex regulatory interplay between the initiation of DNA replication and deoxyribonucleotide synthesis. In Escherichia coli, the ATP-bound DnaA protein initiates chromosomal replication. Upon loading of the beta-clamp subunit (DnaN) of the replicase, DnaA is inactivated as its intrinsic ATPase activity is stimulated by the protein Hda. The beta-subunit acts as a matchmaker between Hda and DnaA. Chain elongation of DNA requires a sufficient supply of deoxyribonucleotides (dNTPs), which are produced by ribonucleotide reductase (RNR). We present evidence suggesting that the molecular switch from ATP-DnaA to ADP-DnaA is a critical step coordinating DNA replication with increased deoxyribonucleotide synthesis. Characterization of dnaA and dnaN mutations that result in a constitutively high expression of RNR reveal this mechanism. We propose that the nucleotide bound state of DnaA regulates the transcription of the genes encoding ribonucleotide reductase (nrdAB). Accordingly, the conversion of ATP-DnaA to ADP-DnaA after initiation and loading of the beta-subunit DnaN would allow increased nrdAB expression, and consequently, coordinated RNR synthesis and DNA replication during the cell cycle.
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PMID:A novel regulatory mechanism couples deoxyribonucleotide synthesis and DNA replication in Escherichia coli. 1648 21

Viruses NY-2A and AR158, members of the family Phycodnaviridae, genus Chlorovirus, infect the fresh water, unicellular, eukaryotic, chlorella-like green alga, Chlorella NC64A. The 368,683-bp genome of NY-2A and the 344,690-bp genome of AR158 are the two largest chlorella virus genomes sequenced to date; NY-2A contains 404 putative protein-encoding and 7 tRNA-encoding genes and AR158 contains 360 putative protein-encoding and 6 tRNA-encoding genes. The protein-encoding genes are almost evenly distributed on both strands, and intergenic space is minimal. Two of the NY-2A genes encode inteins, the large subunit of ribonucleotide reductase and a superfamily II helicase. These are the first inteins to be detected in the chlorella viruses. Approximately 40% of the viral gene products resemble entries in the public databases, including some that are unexpected for a virus. These include GDP-d-mannose dehydratase, fucose synthase, aspartate transcarbamylase, Ca(++) transporting ATPase and ubiquitin. Comparison of NY-2A and AR158 protein-encoding genes with the prototype chlorella virus PBCV-1 indicates that 85% of the genes are present in all three viruses.
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PMID:Sequence and annotation of the 369-kb NY-2A and the 345-kb AR158 viruses that infect Chlorella NC64A. 1702 58

Corynebacteria form an important part of the red smear cheese microbial surface consortium. To gain a better understanding of molecular adaptation due to low pH induced by lactose fermentation, the global gene expression profile of Corynebacterium glutamicum adapted to pH 5.7 with lactic acid under continuous growth in a chemostat was characterized by DNA microarray analysis. Expression of a total of 116 genes was increased and that of 90 genes was decreased compared to pH 7.5 without lactic acid, representing 7% of the genes in the genome. The up-regulated genes encode mainly transcriptional regulators, proteins responsible for export, import, and metabolism, and several proteins of unknown function. As much as 45% of the up-regulated open reading frames code for hypothetical proteins. These results were validated using real-time reverse transcription-PCR. To characterize the functions of 38 up-regulated genes, 36 single-crossover disruption mutants were generated and analyzed for their lactic acid sensitivities. However, only a sigB knockout mutant showed a highly significant negative effect on growth at low pH, suggesting a function in organic-acid adaptation. A sigE mutant already displayed growth retardation at neutral pH but grew better at acidic pH than the sigB mutant. The lack of acid-sensitive phenotypes in 34 out of 36 disrupted genes suggests either a considerable redundancy in acid adaptation response or coincidental effects. Other up-regulated genes included genes for ion transporters and metabolic pathways, including carbohydrate and respiratory metabolism. The enhanced expression of the nrd (ribonucleotide reductase) operon and a DNA ATPase repair protein implies a cellular response to combat acid-induced DNA damage. Surprisingly, multiple iron uptake systems (totaling 15% of the genes induced >or=2-fold) were induced at low pH. This induction was shown to be coincidental and could be attributed to iron-sequestering effects in complex media at low pH.
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PMID:Gene expression analysis of Corynebacterium glutamicum subjected to long-term lactic acid adaptation. 1752 6


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