Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The protein transcription factor IIIA (TFIIIA) is involved in the synthesis of 5S RNA in vitro by RNA polymerase III. It can be isolated from Xenopus laevis oocytes as a 7S particle in which the protein is associated with 5S RNA. Recently it has been shown that the native particle contains 7-11 zinc atoms. Analysis of the amino-acid sequence of TFIIIA revealed nine similar domains of approximately 30 amino acids, each containing two invariant pairs of histidines and cysteines, which have been implicated as possible binding sites for the zinc atoms. Other regulatory proteins with sequence homology to the zinc-binding domains of TFIIIA have now been reported. Here, we report the results of an EXAFS (extended X-ray absorption fine structure) study of TFIIIA which shows that the coordination sphere of the zinc sites consists of two cysteine and two histidine residues.
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PMID:EXAFS study of the zinc-binding sites in the protein transcription factor IIIA. 379 33

Both the single DNA-dependent RNA polymerase found in zinc-deficient (-Zn) Euglena gracilis and the RNA polymerase III from zinc-sufficient (+Zn) cells have been isolated by methods previously used to purify polymerases I and II [Falchuk, K. H., Mazus, B., Ulpino, L., & Vallee, B. L. (1976) Biochemistry 15, 4468; Falchuk, K. H., Mazus, B., Ulpino, L., & Vallee, B. L. (1977) Biochem. Biophys. Res. Commun. 74, 1206]. Like class II polymerases, the enzyme from -Zn organisms elutes from DNA-cellulose and phosphocellulose with 0.6 M NaCl and 0.35 M NH4Cl, respectively. It is inhibited by 8-hydroxyquinoline, 8-hydroxyquinoline-5-sulfonic acid, alpha,alpha'-bipyridyl, dipicolinic acid, and 1,10-phenanthroline (OP); 4,7-phenanthroline, the nonchelating analogue, does not inhibit. The pKI(OP) of this enzyme is identical with that of polymerase II but distinct from those of polymerases I and III. Elemental analysis confirms that zinc is the functional metal while copper, manganese, iron, and magnesium are absent. However, the -Zn enzyme is at least 4 orders of magnitude more resistant to alpha-amanitin (alpha-A) than the class II polymerase. Further, its response to alpha-A is unlike that of either polymerase I or polymerase III. Thus, -Zn cells contain a single, alpha-amanitin-resistant (alpha-Ar) RNA polymerase, whose behavior otherwise resembles that of the alpha-amanitin-sensitive polymerase II.
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PMID:Zinc deficiency and the Euglena gracilis chromatin: formation of an alpha-amanitin-resistant RNA polymerase II. 392 88

The 7S particle of Xenopus laevis oocytes contains 5S RNA and a 40-K protein which is required for 5S RNA transcription in vitro. Proteolytic digestion of the protein in the particle yields periodic intermediates spaced at 3-K intervals and a limit digest containing 3-K fragments. The native particle is shown to contain 7-11 zinc atoms. These data suggest that the protein contains repetitive zinc-binding domains. Analysis of the amino acid sequence reveals nine tandem similar units, each consisting of approximately 30 residues and containing two invariant pairs of cysteines and histidines, the most common ligands for zinc. The linear arrangement of these repeated, independently folding domains, each centred on a zinc ion, comprises the major part of the protein. Such a structure explains how this small protein can bind to the long internal control region of the 5S RNA gene, and stay bound during the passage of an RNA polymerase molecule.
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PMID:Repetitive zinc-binding domains in the protein transcription factor IIIA from Xenopus oocytes. 404 Aug 53

Highly purified preparations of the DNA-dependent RNA polymerase obtained from Escherichia coli contain about 2 g-atoms of tightly bound zinc per mol (molecular weight 370,000) of enzyme. When the purified enzyme is fractionated on Sephadex G-150 or G-200, correlation is observed between the zinc and enzymic activity. Although some of the preparations examined also contain iron, copper, and magnesium, the content of these metal ions show no consistent correlation with RNA polymerase activity. Initiation of RNA synthesis is specifically inhibited by 1,10-phenanthroline. Less-effective inhibition is observed for other chelating agents or for a nonchelating phenanthroline analog. The analog also exhibits a pattern of inhibition differing from that characteristic of 1,10-phenanthroline. Binding of purine nucleoside triphosphates at the lower-affinity (K(d) = 0.15 mM) site may also be prevented by the addition of 1,10-phenanthroline. One or both of the bound zinc atoms may, therefore, participate in the initiation of RNA synthesis.
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PMID:The presence and possible role of zinc in RNA polymerase obtained from Escherichia coli. 494 29

The activity of DNA-dependent RNA polymerase has been measured in liver nuclei from suckling rats nursed by zinc-deficient dams, or by controls that were either pair-fed or given free access to the diet. In the zinc-deficient pups, the activity of the enzyme did not increase; it fell after the tenth day of life.
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PMID:Decreased RNA polymerase activity in mammalian zinc deficiency. 504 77

Reverse transcriptase isolated from avian myeloblastosis virus (AMV) and Rauscher murine leukemia virus (RLV) were examined for their ability to catalyze polymerization, ribonuclease H, pyrophosphate exchange, and pyrophosphorolysis reactions. A detailed characterization and a study of requirements for the expression of pyrophosphate exchange and pyrophosphorolysis reactions indicated that a variety of RNA and DNA template-primers supported these catalytic reactions. Furthermore, hydrogen bonding of template to primer was essential, although RNA:RNA template-primers, e.g. poly(rA) . (rU)9 or 70 S RNA . tRNA complex, were not utilized for these reactions. AMV enzyme required Mg2+, and RLV enzyme Mn2+, as the preferred divalent metal ion for the expression of these activities. Response of various catalytic reactions to site-specific inhibitors revealed that polymerization and pyrophosphate exchange reactions were susceptible to reagents that affected either the substrate or the template binding site, intrinsic zinc, or sulfhydryl groups. RNase H and pyrophosphorolysis activities, on the other hand, exhibited susceptibility only to the template site-specific reagent. We, therefore, conclude that RNase H and pyrophosphorolysis reactions are catalyzed through the template binding site while polymerization and pyrophosphate exchange reactions require additional participation of the substrate binding site, as well as that of intrinsic zinc and the presence of reactive sulfhydryl groups.
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PMID:Enzymatic activities associated with avian and murine retroviral DNA polymerases. Catalysis of and active site involvement in pyrophosphate exchange and pyrophosphorolysis reactions. 615 89

The effects of 14 metal ions (chlorides) on the transcription of calf thymus DNA and phage T4 DNA with Escherichia coli RNA polymerase were tested. These assays were conducted under improved conditions of lower pH and in the absence of 2-mercaptoethanol to permit greater stability of the metal ions in solution. Among the divalent metal ions tested, the concentration-dependent order of inhibition of overall transcription is Pb2+ greater than Zn2+ greater than Cu2+ greater than Be2+ greater than Cd2+ greater than Ni2+ greater than Ca2+ greater than Co2+ greater than Mn2+ greater than Mg2+ greater than Sr2+ and is the same with either template. At pH 7.4 and in the absence of 2-mercaptoethanol, considerably lower concentrations of several of the divalent metal ions are needed for inhibition of overall transcription than at pH 8.1 and in the presence of 2-mercaptoethanol. Ca2+, Mg2+, Sr2+, Zn2+, Li+, Na+, and K+--considered to be non-mutagenic and non-carcinogenic--decrease chain initiation (measured with T4 DNA) at concentrations that inhibit overall transcription. Pb2+, Cd2+, Co2+, Be2+, and Mn2+--all mutagenic or carcinogenic--stimulate chain initiation (although at widely different rates) at concentrations that inhibit overall transcription. Cu2+ and Ni2+--both carcinogenic--stimulate initiation only at very low concentrations, followed by a progressive decrease in initiation at concentrations that inhibit overall transcription.
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PMID:Selective effects of metal ions on RNA synthesis rates. 617 51

The Pb2+ and Zn2+ ions are efficient catalysts for the polycytidylic acid-directed polymerization of an activated guanylic acid derivative, guanosine 5'-phosphorimidazolide. The products include oligomers of 30 to 40 units in length. The nucleotide residues are predominantly 2'-5' linked when Pb2+ is the catalyst, and predominantly 3'-5' linked in the presence of Zn2+. The significance of these results in the context of the prebiotic evolution of RNA polymerase is discussed.
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PMID:Efficient metal-ion catalyzed template-directed oligonucleotide synthesis. 624 62

Zinc forms part of the active site and/or stabilizes the conformation of several enzymes. The protein metallothionein constitutes a zinc deposit from which the metal is transferred to enzymes. Zinc participates in the synthesis of nucleic acids and hence in the synthesis of proteins, principally through multi-enzyme pir 1-3 and DNA-dependent RNA polymerase, which are metallo-enzymes of zinc. Zinc is therefore necessary for normal growth, development, healing and ossification.
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PMID:Biochemistry of zinc. 635 5

During the past two decades, the essentiality of zinc for man has been established. Deficiency of zinc in man due to nutritional factors and several diseased states has been recognized. High phytate content of cereal proteins decreases availability of zinc; thus the prevalence of zinc deficiency is likely to be high in a population subsisting mainly on cereal proteins. Alcoholism is known to cause hyperzincuria and thus may play a role in producing zinc deficiency in man. Malabsorption, cirrhosis of the liver, chronic renal disease and other chronically debilitating diseases may similarly induce zinc deficiency in human subjects. A severe deficiency of zinc has recently been recognized to occur in patients with sickle cell anemia and a beneficial effect of zinc therapy in such patients has been reported. Growth retardation, male hypogonadism, skin changes, poor appetite, mental lethargy and delayed wound healing are some of the manifestations of chronically zinc-deficient human subjects. Taste abnormalities, correctable with zinc supplementation, have been observed in uremic subjects. Recently, abnormal dark adaptation related to zinc deficiency in patients with cirrhosis of the liver and sickle cell disease has been reported. In severely zinc-deficient patients, dermatological manifestations, diarrhea, alopecia, mental disturbances and intercurrent infections predominate and if untreated the condition becomes fatal. Zinc deficiency is known to affect testicular functions adversely in man and animals. This effect of zinc is at the end organ level and it appears that zinc is essential for spermatogenesis and testosterone steroidogenesis. Zinc is involved in many biochemical functions. Several zinc metalloenzymes have been recognized in the past decade. Zinc is required for each step of cell cycle in microorganisms and is essential for DNA synthesis. Thymidine kinase, RNA polymerase, DNA-polymerase from various sources and RNA-dependent DNA polymerase from viruses have been shown to be zinc-dependent enzymes. Zinc also regulates the activity of RNase; thus the catabolism of RNA appears to be zinc-dependent. The effect of zinc on protein synthesis may be attributable to its vital role in nucleic acid metabolism. The activities of many zinc-dependent enzymes have been shown to be affected adversely in zinc-deficient tissues. Three enzymes, alkaline phosphatase, carboxypeptidase and thymidine kinase, appear to be most sensitive to zinc restriction in that their activities are affected adversely within three to six days of institution of a zinc-deficient diet to experimental animals.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Zinc deficiency in human subjects. 636 78


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