Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.1.25 (triphosphatase)
 1,529 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nuclear envelopes contain a nucleoside triphosphatase which is thought to be involved in the supply of energy for nucleo-cytoplasmic RNA transport. This enzyme is stimulated most efficiently by poly(A) and to a lesser extent by poly(G) and poly(dT). Half-maximal stimulation of the enzyme from rat liver nuclei, which was associated with the poly(A)-specific Endoribonuclease IV and was free from poly(A) polymerase and Endoribonuclease V activity, was determined to occur at a concentration of 1.1 X 10(6) poly(A) molecules/nuclear ghost. Double-reciprocal plot analysis revealed a 2.8-fold stimulation of the enzyme by poly(A). Poly(A) in the hybrid form had no influence on the activity of the nucleoside triphosphatase. Stimulation by oligo(A) required a minimal chain length of 18 nucleotide units. Naturally occurring RNA species enhanced the nucleoside triphosphatase activity, provided they contained a poly(A) segment. Using poly(A)(+)mRNA, half-maximal stimulation was determined to proceed at 0.5 X 10(6) molecules/nuclear ghost. Removal of the poly(A) segment from mRNA mRNA abolished the stimulatory effect on the enzyme. Microtubule protein was found to inhibit the nucleoside triphosphatase efficiently. At a concentration of 2.0 mg/ml, polymerized microtubule protein reduced the enzyme activity by 96%. Dimeric tubulin was less inhibitory, while actin was without any significant effect. From these findings it is suggested that a possible nucleoside triphosphatase-mediated transport of poly(A)(+) mRNA through nuclear envelope is controlled firstly, by the poly(A) segment of this RNA species and secondly, by cytoplasmic microtubules.
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PMID:Nuclear-envelope nucleoside triphosphatase: stimulation by poly(A) (+)mRNA and modulation by microtubule protein. 613 59

The RNA-stimulated nucleoside triphosphatase (NTPase) and helicase of hepatitis C virus (HCV) consists of three domains with highly conserved NTP binding motifs located in the first domain. The ATP-binding domain was obtained by limited proteolysis of a greater fragment of the HCV polyprotein, and it was purified to homogenity by column chromatography. The identity of the domain, comprising amino acids 1203 to 1364 of the HCV polyprotein, was confirmed by N- and C-terminal sequencing and by its capability to bind 5'-fluorosulfonylbenzoyladenosine (FSBA). The analyses of the kinetics of ATP binding revealed a single class of binding site with the Kd of 43.6 microM. The binding is saturable and dependent on Mn2+ or Mg2+ ions. Poly(A) and poly(dA) show interesting properties as regulators of the ATP-binding capacity of the domain. Polynucleotides bind to the domain and enhance its affinity for ATP. In addition, ATP enhances the affinity of the domain for the polynucleotides. Different compounds, which are known to interact with nucleotide binding sites of various classes of enzymes, were tested for their ability to inhibit the binding of ATP to the domain. Of the compounds tested, two agents behaved as inhibitors: paclitaxel, which inhibits the ATP binding competitively (IC50 = 22 microM), and trifluoperazine, which inhibits the ATP binding by a noncompetitive mechanism (IC50 = 98 microM). Kinetic experiments with the NTPase/helicase indicate that both compounds inhibit the NTPase activity of the holoenzyme by interacting with its ATP-binding domain.
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PMID:Biochemical properties of a minimal functional domain with ATP-binding activity of the NTPase/helicase of hepatitis C virus. 1058 65