Subunit structure of l-asparaginase from Escherichia coli B

Kirchbaum, Joel; Wriston, John C.; Ratych, Oleh T.

doi:10.1016/0005-2795(69)90191-3

Cited by 32 publications

(14 citation statements)

References 27 publications

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“…From these results, together with the data by Kirschbaum et al [12], it can be said that the asparaginase molecule dissociates into subunits, accompanied by loss of the enzymic activity. The stabilization of asparaginase may be due to the protection from dissociation of the molecule into subunits with Fab.…”

Section: Resultssupporting

confidence: 54%

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Activation and stabilization of asparaginase by anti‐asparaginase IgG and its Fab

et al. 1985

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Modified asparaginase, in which 4 tryptophan residues were modified with 2-hydroxy-S-nitrobenzyl bromide, had little enzymic activity and retained immunoreactivity ((1976) FEBS Lett. 65, 11-t 51. Addition of IgG or its Fab towards asparaginase to the modified asparaginase gave rise to marked enhancement of the enzymic activity. Native asparaginase (4 subunits) lost the enzymic activity due to dissociation into subunits by dilution of the enzyme solution. However. in the presence of Fab, asparaginase did not lose enzymic activity on dilution, probably due to no dissociation into subunits occurring.

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Section: Resultssupporting

confidence: 54%

“…Kirschbaum et al [12] reported that the asparaginase molecule (8.6 S) is dissociated into subunits (5.6 S and 4.0 S) by the dilution of an asparaginase solution. Here, we studied the dilution effect on the enzymic activity of asparaginase in the presence and absence of Fab.…”

Section: Resultsmentioning

confidence: 99%

Activation and stabilization of asparaginase by anti‐asparaginase IgG and its Fab

et al. 1985

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“…Later this inhibition was shown by Broome 21 to be due to the L-asparaginase act1v1ty. A number of other asparaginases, such as those from Escherichia coli and other bacteria 3 ' 41 have recently been found to inhibit tumors, as first shown by Mashburn and Wriston.…”

mentioning

confidence: 92%

l-Asparaginase fromE. coli

Nakamura¹,

Morikawa²,

Fujio³

et al. 1971

Agricultural and Biological Chemistry

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“…Changes in the oligomeric form of l ‐asparaginase could be clinically important and may require further investigation. Earlier studies have shown that EcAII is able to form oligomers of different molecular masses, depending on the enzyme concentration and the influence of various chemicals [28].…”

Section: Resultsmentioning

confidence: 99%

Structural and functional insights into Erwinia carotovora l‐asparaginase

et al. 2008

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Bacterial l‐asparaginases are enzymes that catalyze the hydrolysis of l‐asparagine to aspartic acid. For the past 30 years, these enzymes have been used as therapeutic agents in the treatment of acute childhood lymphoblastic leukemia. Their intrinsic low‐rate glutaminase activity, however, causes serious side‐effects, including neurotoxicity, hepatitis, coagulopathy, and other dysfunctions. Erwinia carotovora asparaginase shows decreased glutaminase activity, so it is believed to have fewer side‐effects in leukemia therapy. To gain detailed insights into the properties of E. carotovora asparaginase, combined crystallographic, thermal stability and cytotoxic experiments were performed. The crystal structure of E. carotovoral‐asparaginase in the presence of l‐Asp was determined at 2.5 Å resolution and refined to an Rcryst of 19.2 (Rfree = 26.6%) with good stereochemistry. Cytotoxicity measurements revealed that E. carotovora asparaginase is 30 times less toxic than the Escherichia coli enzyme against human leukemia cell lines. Moreover, denaturing experiments showed that E. carotovora asparaginase has decreased thermodynamic stability as compared to the E. coli enzyme and is rapidly inactivated in the presence of urea. On the basis of these results, we propose that E. carotovora asparaginase has limited potential as an antileukemic drug, despite its promising low glutaminase activity. Our analysis may be applicable to the therapeutic evaluation of other asparaginases as well.

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Subunit structure of l-asparaginase from Escherichia coli B

Cited by 32 publications

References 27 publications

Activation and stabilization of asparaginase by anti‐asparaginase IgG and its Fab

Activation and stabilization of asparaginase by anti‐asparaginase IgG and its Fab

l-Asparaginase fromE. coli

Structural and functional insights into Erwinia carotovora l‐asparaginase

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