Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
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Query: EC:2.7.7.48 (
transcriptase
)
9,479
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Mutagenic heterocyclic amines are metabolized to mutagens which act directly on Salmonella typhimurium by P-448 forms of cytochrome P-450. These direct mutagens are N-hydroxylated heterocyclic amines, such as N-hydroxy-Trp-P-1, N-hydroxy-Trp-P-2, N-hydroxy-Glu-P-1, N-hydroxy-Glu-P-2, N-hydroxy-IQ, N-hydroxy-2-amino-alpha-carboline (N-hydroxy-A alpha C), and N-hydroxy-2-amino-3-methyl-alpha-carboline (N-hydroxy-MeA alpha C). The treatment of rats with polychlorinated biphenyl stimulated N-hydroxylation of heterocyclic amines about 10- to 260-fold depending on the substrates used. The N-hydroxylation activities of purified cytochrome P-448-H and P-448-L were markedly different. P-448-H, which had very low activity for benzo[a] pyrene metabolic activation, showed high N-hydroxylation activity. The activity ratio P-448-H:P-448-L was markedly different depending on the amines used. This ratio was 45, 22, 3, and 0.02, respectively, for Glu-P-1, IQ, Trp-P-2, and benzo[a] pyrene. On the other hand, N-acetylation of the heterocyclic amines was very low. Although marked species differences in the N-acetylation were observed, the activities of the heterocyclic amines were about 1/100 of that of 2-aminofluorene. N-Hydroxy-Trp-P-2 could react directly to DNA, but N-hydroxy-Glu-P-1 could not. Therefore we need to consider the presence of a further activating system in mammalian and bacterial cells. We observed that N-hydroxy-Trp-P-2 was activated by prolyl-t-
RNA synthetase
, but N-hydroxy-Glu-P-1 was not activated by the same system. In the bacterial cells, both N-hydroxy-Trp-P-2 and N-hydroxy-Glu-P-1 were not activated by prolyl-t-
RNA synthetase
. However, both hydroxylamines were activated by the
acetyl-CoA
-dependent mechanism in mammalian and bacterial cells. These results indicated that the O-acetylation is an important pathway for DNA damage by heterocyclic amines in chemical carcinogenesis.
...
PMID:Metabolic activation of mutagenic heterocyclic aromatic amines from protein pyrolysates. 351 87
The PA, PB1, and PB2 subunits, components of the
RNA-dependent RNA polymerase
of influenza A virus, are essential for viral transcription and replication. The PB2 subunit binds to the host RNA cap (7-methylguanosine triphosphate (m(7)GTP)) and supports the endonuclease activity of PA to "snatch" the cap from host pre-mRNAs. However, the structure of PB2 is not fully understood, and the functional sites remain unknown. In this study, we describe a novel Val/Arg/Gly (VRG) site in the PB2 cap-binding domain, which is involved in interaction with
acetyl-CoA
found in eukaryotic histone acetyltransferases (HATs). In vitro experiments revealed that the recombinant PB2 cap-binding domain that includes the VRG site interacts with
acetyl-CoA
; moreover, it was found that this interaction could be blocked by CoA and various HAT inhibitors. Interestingly, m(7)GTP also inhibited this interaction, suggesting that the same active pocket is capable of interacting with
acetyl-CoA
and m(7)GTP. To elucidate the importance of the VRG site on PB2 function and viral replication, we constructed a PB2 recombinant protein and recombinant viruses including several patterns of amino acid mutations in the VRG site. Substitutions of the valine and arginine residues or of all 3 residues of the VRG site to alanine significantly reduced the binding ability of PB2 to
acetyl-CoA
and its RNA polymerase activity. Recombinant viruses containing the same mutations could not be replicated in cultured cells. These results indicate that the PB2 VRG sequence is a functional site that is essential for
acetyl-CoA
interaction, RNA polymerase activity, and viral replication.
...
PMID:A novel functional site in the PB2 subunit of influenza A virus essential for acetyl-CoA interaction, RNA polymerase activity, and viral replication. 2506 5
The PA, PB1, and PB2 subunits, components of the
RNA-dependent RNA polymerase
of influenza A virus, and the nucleoprotein (NP) interact with the genomic RNA of influenza viruses and form ribonucleoproteins. Especially, the PB2 subunit binds to the host RNA cap [7-methylguanosine triphosphate (m
7
GTP)] and supports the endonuclease activity of PA to "snatch" the cap from host pre-mRNAs. In this study, we describe a novel Val/Arg/Gly (VRG) site in the PB2 cap-binding domain, which is necessary for interaction with
acetyl-CoA
found in eukaryotic histone acetyltransferases (HATs). In vitro experiments revealed that the recombinant PB2 cap-binding domain that includes the VRG site interacts with
acetyl-CoA
; moreover, it was found that this interaction could be blocked by CoA and various HAT inhibitors. Interestingly, m
7
GTP also inhibited this interaction, suggesting that the same active pocket is capable of interacting with
acetyl-CoA
and m
7
GTP. To elucidate the importance of the VRG site on PB2 function and viral replication, we constructed a PB2 recombinant protein and recombinant viruses including several patterns of amino acid mutations in the VRG site. Substitutions of 2 or 3 amino acid residues of the VRG site to alanine significantly reduced PB2's binding ability to
acetyl-CoA
and its RNA polymerase activity. Recombinant viruses containing the same mutations could not be replicated in cultured cells. These results indicate that the PB2 VRG sequence is a functional site that is essential for
acetyl-CoA
interaction, RNA polymerase activity, and viral replication. I will also discuss some novel functions of NP in this review.
...
PMID:Structural and Biochemical Analyses on the RNA-dependent RNA Polymerase of Influenza Virus for Development of Novel Anti-influenza Agents. 2815 33
The production of secondary metabolites, while important for bioengineering purposes, presents a paradox in itself. Though widely existing in plants and bacteria, they have no definite physiological roles. Yet in both native habitats and laboratories, their production appears robust and follows apparent metabolic switches. We show in this work that the enzyme-catalysed process may improve the metabolic stability of the cells. The latter can be responsible for the overall metabolic behaviours such as dynamic metabolic landscape, metabolic switches and robustness, which can in turn affect the genetic formation of the organism in question. Mangrove-derived
Streptomyces xiamenensis
318, with a relatively compact genome for secondary metabolism, is used as a model organism in our investigation. Integrated studies via kinetic metabolic modelling,
transcriptase
measurements and metabolic profiling were performed on this strain. Our results demonstrate that the secondary metabolites increase the metabolic fitness of the organism via stabilizing the underlying metabolic network. And the fluxes directing to NADH, NADPH,
acetyl-CoA
and glutamate provide the key switches for the overall and secondary metabolism. The information may be helpful for improving the xiamenmycin production on the strain.
...
PMID:Dynamical modelling of secondary metabolism and metabolic switches in
Streptomyces xiamenensis
318. 3131 9
