Author/Authors :
Amani Jafar نويسنده , Sedighian Hamid نويسنده Applied Microbiology Research Center, Baqiyatallah University Of Medical Sciences,Tehran, I.R. Iran , Bambai Bijan نويسنده National Institute of Genetic Engineering and Biotechnology (NIGEB),Tehran,Iran , Mahboobi Mahdieh نويسنده Applied Microbiology Research Center, Baqiyatallah
University of Medical Sciences, Tehran, IR Iran , Hedayati CH Mojtaba نويسنده Department of Microbiology, Parasitology and Immunology,
Guilan University of Medical Sciences, Rasht, Guilan, IR
Iran , Esmaeil Soofian Saeed نويسنده Department of Internal Medicine Faculty of Medicine, Iran
University of Medical Sciences, Tehran, IR Iran
Abstract :
Background Asparginase is known to be one of the most important
bedrocks of acute lymphoblastic leukemia (ALL) treatment in almost all
pediatric regimens in treatment protocols. Escherichia
coli L-Asparginase (EC 3.5.1.1) is one of the most common
resources to produce this enzyme. One of the affordable methods to
overcome the side effects of drug is utilizing bioinformatic tools in
the form of In silico study. In this study we designed a new structure
of L-Asparginase to decrease its toxicity, reduce some side effects and
increase the stability. Methods We used some bioinformatics software and
servers like Toxin red, Popmusic, kobami and I-TASSER server to reduce
toxicity level of enzyme, and to increase stability and enzyme
half-life. Results We obtained 6 protein sequences in which the best was
Mut 6 with four changes in structure: L23G, K129L, S263C and R291F. In
contrast to the wild type, the new predicted protein is not toxic and
has 25 hours more half-life and 600 kcal/mol more stable with no
significant change in protein secondary, tertiary structure,
antigenicity and allergenicity. Conclusions Finally, sequence number 6
was the only sequence with all distinct characteristics: non-toxic, more
stability and more half life.
