Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.1.1 (asparaginase)
 2,695 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An intracellular L-asparaginase with antitumour activity was purified from a strain of Citrobacter. The optimum conditions for enzyme production by fermentation on scales up to 2700 l were investigated. Highest enzyme yield was obtained in corn-steep liquor medium (9-2%, W/V) at 37 degrees C. Oxygen limitation was not necessary for high enzyme yield. A total recovery of 4-3% from nucleic-acid-free extract and a 180-fold increase in specific activity were obtained after purificaiton. The specific activity of the purified preparation was 45 i.u./mg protein. The enzyme hydrolysed D-asparagine and L-glutamine at 7 and 5%, respectively, of its activity toward L-asparagine, but L-glutaminase activity could be demonstrated only at substrate concentrations above 5 mM. The Km values for L-asparagine and D-asparagine were 2-6 X 10(-5) and 1-4 X 10(-4) respectively. The anti-lymphoma activity of the enzyme was demonstrated with Gardner lymphosarcoma and was found only slightly less potent that Crasnitin, the most active asparaginase so far tested in this system.
J Gen Microbiol 1975 Nov
PMID:The properties and large-scale production of L-asparaginase from citrobacter. 0 Apr 65

Rabbit antisera against L-asparaginase preparations from Escherichia coli, Erwinia carotovora, Citrobacter sp. and Chromobacterium violaceum showed on immunoelectrophoresis that only the enzymes from E. coli and Citrobacter are immunologically related. Purified preparations had to be used to determine the immunological cross-reactions. Immunoelectrophoresis at different pH values yielded the zero mobility points of the enzymes. The activity of the Er. carotovora preparation was enhanced up to fourfold by homologous antiserum but not by normal sera. Heterologous antisera also enhanced, but only at a higher concentration. Less enhancement was observed for the other enzymes with antisera as well as with bovine serum albumin. Inhibition was not observed.
J Gen Microbiol 1976 Jan
PMID:Immunological relationships of bacterial L-asparaginases. 5 4

Studies in mice of the modes of immunomodification imposed by cyclophosphamide, have been extended to comparative studies with Myocrisin, 1-asparaginase and interferon. It has been shown for mice infected i.p. or i.c. by an avirulent clone of SFV, that the potentiation of disease may be marked by many distinct changes in the type of rate of response. For low i.p. doses of virus, enhancement (Myocrisin, 1-asparaginase) or impairment (interferon) of the efficiency of infection may be associated with death (potentiation by Myocrisin) or protection (immunoenhancement by 1-asparaginase). For higher doses of virus the increased mortality after infection (primary potentiation) is determined within 2 or 3 days and appears to be due to inhibition of phagocytosis (Myocrisin and 1-asparaginase) and of T cell functions (1-asparaginase and cyclophosphamide). The increased incidence of death after challenge (secondary potentiation) appears to be due to inhibition of B cell functions (cyclophosphamide) associated with suppression of antibody synthesis and persistence of viraemia. These results are discussed in relation to the expression of virulence by a heterogeneous and replicating antigen. The critical cellular and humoral changes which occur within 2 or 3 days of infection are emphasized.
J Gen Virol 1975 Aug
PMID:Immunomodification and the expression of virulence in mice by defined strains of Semliki Forest virus: the effects of myocrisin and 1-asparaginase. 80 43

The plasmid RP4::Mu cts62 in stably inherited by Erwinia carotovora 268 strain. Under the conditions of thermoinduction bacteriophage Mu is segregated and completely eliminated more intensively than in Escherichia coli cells. At thermoinduction the transposition of bacteriophage Mu cts62 into different chromosomal sites takes place, causing the induction of chlorate resistant and auxotrophic mutants with the frequency of 10(-4). Two clones deficient in production of 2 of the 4 resident prophages of Erwinia carotovora 268 strain were found among Mu-induced mutants. The deleted prophages are E105 and 59. DNA-DNA hybridization has revealed the complete and partial deletions of bacteriophage E105 with the level of L-asparaginase production in the cells remaining intact. The damage of the prophage 59 is probably caused by point mutations or short deletions.
Mol Gen Mikrobiol Virusol
PMID:[Mu-induced deletions and mutations of Erwinia carotovora chromosomes, including resident prophages E105 and 59]. 140 59

Glutamine depletion strongly inhibits the replication of Rauscher murine leukaemia retrovirus (RLV) in vitro. Pseudomonas 7A glutaminase-asparaginase (PGA), capable of depleting glutamine and asparagine for prolonged periods, was used to determine the therapeutic effectiveness of glutamine depletion in mice infected with RLV or Friend virus. During PGA treatment of viraemic animals, serum reverse transcriptase activity fell to control levels and infected animals did not develop splenomegaly. The therapeutic results obtained with PGA compared favourably with those of azidothymidine given intraperitoneally at 30 mg/kg/day. Western blots performed on splenic tissue from control and treated animals indicated that glutamine depletion prevented readthrough of an amber codon at the gag-pol junction, stopping translation of viral mRNA at that point. Treatment of RLV-infected animals with PGA resulted in nearly a 200% increase in mean survival time even when therapy was initiated late in the course of the disease. To our knowledge, this is the first demonstration that a nutrient required for viral replication can be enzymically depleted in vivo to inhibit viral replication.
J Gen Virol 1991 Feb
PMID:Inhibition of mouse retroviral disease by bioactive glutaminase-asparaginase. 170 10

A high L-asparaginase (L-asparagine amidohydrolase: EC 3.5.1.1) activity was found under conditions of lysine overproduction in cultures of Corynebacterium glutamicum. L-Asparaginase was purified 98-fold by protamine sulphate precipitation. DEAE-Sephacel anion exchange, ammonium sulphate precipitation and Sephacryl S-200 gel filtration. The asparaginase protein was subjected to PAGE under non-denaturing conditions, identified by an in situ reaction and eluted from the gel in an active form. The estimated Mr from gel filtration and SDS-PAGE was 80,000. The L-asparaginase activity was inhibited by the L-asparagine analogue 5-diazo-4-oxo-L-norvaline. Neither D-asparagine nor L-glutamine was a substrate for the enzyme. L-Asparaginase was produced constitutively: its role may be that of an overflow enzyme, converting excess asparagine into aspartic acid, the direct precursor of lysine and threonine.
J Gen Microbiol 1990 Mar
PMID:Characterization and partial purification of L-asparaginase from Corynebacterium glutamicum. 239 90

A genomic library of Erwinia chrysanthemi DNA was constructed in bacteriophage lambda 1059 and recombinants expressing Er. chrysanthemi asparaginase detected using purified anti-asparaginase IgG. The gene was subcloned on a 4.7 kb EcoRI DNA restriction fragment into pUC9 to generate the recombinant plasmid pASN30. The position and orientation of the asparaginase structural gene was determined by subcloning. The enzyme was produced at high levels in Escherichia coli (5% of soluble protein) and was shown to be exported to the periplasmic space. Purified asparaginase from E. coli cells carrying pASN30 was indistinguishable from the Erwinia enzyme on the basis of specific activity [660-700 units (mg protein)-1], pI value (8.5), and subunit molecular weight (32 X 10(3]. Expression of the cloned gene was subject to glucose repression in E. coli but was not significantly repressed by glycerol. Recombinant plasmids, containing the asparaginase gene, when introduced into Erwinia carotovora, caused increased synthesis of the enzyme (2-4 fold higher than the current production strain).
J Gen Microbiol 1986 Jan
PMID:Cloning and expression of the Erwinia chrysanthemi asparaginase gene in Escherichia coli and Erwinia carotovora. 301 58

Of five amidohydrolase activities subject to nitrogen metabolite repression in Aspergillus nidulans, L-asparaginase shows clearest evidence of also being subject to repression by atmospheric oxygen. Such oxygen repressibility is only evident under nitrogen metabolite derepressed conditions. Asparaginase levels are also considerably elevated by areA300, an altered function allele of the positive acting wide domain regulatory gene areA mediating nitrogen metabolite repression and are drastically reduced by loss of function mutations in areA. A. nidulans has two L-asparaginase enzymes and it has been shown by the use of appropriate mutants that these regulatory effects are exerted on the expression of that specified by the ahrA gene but probably not that specified by the apnA gene.
Mol Gen Genet 1988 May
PMID:An asparaginase of Aspergillus nidulans is subject to oxygen repression in addition to nitrogen metabolite repression. 304 73

A temperature-sensitive Escherichia coli mutant defective for the ability to utilize L-asparagine as a sole nitrogen source was isolated after N-methyl-N'-nitro-N-nitrosoguanidine mutagenesis. The mutation (asu) produces two distinct phenotypic effects. Mutant strains grow poorly at high temperature on minimal plates containing asparagine as the sole nitrogen source; this effect is greatly exacerbated by the presence of methionine. Mutant strains utilize L-asparagine as a nitrogen source three to four times more efficiently at permissive temperatures than the wild-type strains. The mutation maps at 32.4 min on the E. coli chromosome, within the E. coli cotransduction gap. Mutant strains produce normal amounts of thermo-stable L-asparaginase I activity. The mutation therefore affects a component of the asparagine utilization system other than the catabolism of asparagine within the cell; it probably affects asparagine uptake.
J Gen Microbiol 1985 Aug
PMID:Identification of a new locus in the Escherichia coli cotransduction gap that represents a new genetic component of the L-asparagine utilization system. 390 41

An amber mutation (glnA3711), the first nonsense mutation isolated in Klebsiella aerogenes, is described. When amber suppressors were present, the mutant made active glutamine synthetase which was more thermolabile than wild type, showing that glnA3711 lies in the structural gene for glutamine synthetase. Strains carrying the glnA3711 allele were unable to express nitrogen regulation of genes coding for histidase, asparaginase, and glutamate dehydrogenase unless amber suppressors were also present. These results support a model that expression of gene(s) from the glnA promoter is required for nitrogen regulation in K. aerogenes.
Mol Gen Genet 1982
PMID:A nonsense mutation in the structural gene for glutamine synthetase leading to loss of nitrogen regulation in Klebsiella aerogenes. 612 65


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