Biochemical properties of yeast l-asparaginase

Jones, Gary E.; Mortimer, Robert

doi:10.1007/bf00487443

Cited by 27 publications

(22 citation statements)

References 20 publications

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“…However, it has high molecular similarity to bacterial enzymes used in therapy1415 and is classified in the bacterial type II family116. In the 1970s, the few studies performed with ScASNase1 demonstrated low activity and affinity to L-Asn1417. Since then, no studies about this enzyme have been reported.…”

mentioning

confidence: 99%

Recombinant L-asparaginase 1 from Saccharomyces cerevisiae: an allosteric enzyme with antineoplastic activity

Costa

Schultz

Pedra

et al. 2016

Sci Rep

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L-asparaginase (L-ASNase) (EC 3.5.1.1) is an important enzyme for the treatment of acute lymphoblastic leukaemia. Currently, the enzyme is obtained from bacteria, Escherichia coli and Erwinia chrysanthemi. The bacterial enzymes family is subdivided in type I and type II; nevertheless, only type II have been employed in therapeutic proceedings. However, bacterial enzymes are susceptible to induce immune responses, leading to a high incidence of adverse effects compromising the effectiveness of the treatment. Therefore, alternative sources of L-ASNase may be useful to reduce toxicity and enhance efficacy. The yeast Saccharomyces cerevisiae has the ASP1 gene responsible for encoding L-asparaginase 1 (ScASNase1), an enzyme predicted as type II, like bacterial therapeutic isoforms, but it has been poorly studied. Here we characterised ScASNase1 using a recombinant enzyme purified by affinity chromatography. ScASNase1 has specific activity of 196.2 U/mg and allosteric behaviour, like type I enzymes, but with a low K0.5 = 75 μM like therapeutic type II. We showed through site-directed mutagenesis that the T64-Y78-T141-K215 residues are involved in catalysis. Furthermore, ScASNase1 showed cytotoxicity for the MOLT-4 leukemic cell lineage. Our data show that ScASNase1 has characteristics described for the two subfamilies of l-asparaginase, types I and II, and may have promising antineoplastic properties.

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mentioning

confidence: 99%

Recombinant L-asparaginase 1 from Saccharomyces cerevisiae: an allosteric enzyme with antineoplastic activity

Costa

Schultz

Pedra

et al. 2016

Sci Rep

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“…One of these enzymes, asparaginase I, is synthesized constitutively and is located within the cell. 10) The other enzyme, asparaginase I L is a mannan glycoprotein in the cell wall and functions in the hydrolysis of extracellular asparagine. 4 ,ll) Intracellular enzymes have the disadvantage that it is necessary to disrupt cells and separate the disrupted cells to recover the enzymes.…”

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confidence: 99%

Extraction of ExtracellularL-Asparaginase fromCandida utilis

Kil

Kim

Park

1995

Bioscience, Biotechnology, and Biochemistry

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“…Minimal medium with vitamins (MV; Jones & Mortimer, 1973), sterilized by filtration, was used for cell propagation. In this medium, nitrogen is present as free ammonium ion (75 mM).…”

Section: E T H O D Smentioning

confidence: 99%

“…L-Asparagine degradation is accomplished by two distinct forms of asparaginase (L-asparagine amidohydrolase, EC 3.5.1 .1) in this species. L-Asparaginase I is synthesized constitutively and is active only on intracellular L-asparagine (Jones & Mortimer, 1973). Asparaginase 11, which has been extensively characterized by its discoverers (Dunlop & Roon, 1975;Dunlop et al, 1976Dunlop et al, , 1978, is a glycoprotein that can deamidate both L-and D-asparagine when they are external to the cell.…”

Section: Introductionmentioning

confidence: 99%

Asparaginase II of Saccharomyces cerevisiae: Dynamics of Accumulation and Loss in Rapidly Growing Cells

Pauling¹,

Jones²

1980

Microbiology

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Asparaginase I1 activity in Saccharomyces cerevisiae can be derepressed in stationary phase cells by nitrogen starvation in the presence of an energy source. We have found that high activity of this enzyme is present in early-exponential phase cells even in the presence of abundant nitrogen. In growing cells that contain high asparaginase I1 activity, further derepression by nitrogen results in the rapid appearance of additional activity. Rapid loss of activity occurs as cultures begin to emerge from exponential growth. Synthesis of protein is required just before loss of activity occurs. Supplementing cultures with L-asparagine or L-glutamine strongly affects the kinetics of loss of activity. Mutation in ASP2 or ASP.?, which results in inability to derepress this enzyme in stationary phase cells, also prohibits the development of the enzyme in exponentially growing cells.

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Biochemical properties of yeast l-asparaginase

Cited by 27 publications

References 20 publications

Recombinant L-asparaginase 1 from Saccharomyces cerevisiae: an allosteric enzyme with antineoplastic activity

Recombinant L-asparaginase 1 from Saccharomyces cerevisiae: an allosteric enzyme with antineoplastic activity

Extraction of ExtracellularL-Asparaginase fromCandida utilis

Asparaginase II of Saccharomyces cerevisiae: Dynamics of Accumulation and Loss in Rapidly Growing Cells

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