Development of Escherichia coli asparaginase II for the Treatment of Acute Lymphocytic Leukemia: In Silico Reduction of asparaginase II Side Effects by a Novel Mutant (V27F)

Document Type : Research Articles

Authors

1 Department of Microbiology, Science and Research Branch, Islamic Azad University, Tehran, Iran.

2 Department of Microbiology, Faculty of Science, North Branch, Islamic Azad University, Tehran, Iran.

3 Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.

Abstract

Acute lymphoblastic leukemia (ALL) is a common blood disease in children that is accountable for many deaths. Due to major improvements in treatment procedures in the past 50 years, the survivability of this disease has risen dramatically to about 90 percent today. L-asparaginase (ASNase) has been used to treat ALL. The glutaminase (GLNase) activity of this enzyme causes some side effects and is unnecessary for anticancer activity. This study investigated mutagenesis in Escherichia coli ASNase II to find a mutant with lower GLNase activity via molecular dynamics (MD) simulation. Residues with low binding energy to asparagine (Asn) and high binding energy to glutamine (Gln) were chosen for mutagenesis. A mutant with low free binding energy to Gln was then selected for molecular docking and MD studies. The results showed that V27F is a good candidate for reducing GLNase activity and that it has little effect on enzyme ASNase activity. A simulation analysis showed that the V27F mutant was more stable than the WT ASNase and that mutagenesis was quite successful.

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Volume 22, Issue 4
April 2021
Pages 1137-1147
  • Receive Date: 12 December 2020
  • Revise Date: 16 March 2021
  • Accept Date: 31 March 2021
  • First Publish Date: 01 April 2021