Applying Bioinformatic Tools for Modeling and Modifying Type II E. coli l-Asparginase to Present a Better Therapeutic Agent/Drug for Acute Lymphoblastic Leukemia.

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 afford...

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Published in:International Journal of Cancer Management Vol. 10; no. 3; pp. 1 - 11
Main Authors: Mahboobi, Mahdieh, Sedighian, Hamid, Hedayati C. H., Mojtaba, Bambai, Bijan, Soofian, Saeed Esmaeil, Amani, Jafar
Format: pictorial research tables/charts Journal Article
Published: Medical Journals Commission of the Ministry of Health & Medical Education Mar2017
Online Access:View this record in EBSCOhost
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      dt: Mar2017
      vid: 10
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      pub: Medical Journals Commission of the Ministry of Health & Medical Education
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        10.5812/ijcm.5785
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        atl: Applying Bioinformatic Tools for Modeling and Modifying Type II E. coli l-Asparginase to Present a Better Therapeutic Agent/Drug for Acute Lymphoblastic Leukemia.
      aug:
        au:
          Mahboobi, Mahdieh
          Sedighian, Hamid
          Hedayati C. H., Mojtaba
          Bambai, Bijan
          Soofian, Saeed Esmaeil
          Amani, Jafar
        affil: Applied Microbiology Research Center, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
      sug:
        subj:
          Bioinformatics
          Leukemia, Lymphocytic, Acute Therapy
          Asparaginase Therapeutic Use
          Antineoplastic Agents Therapeutic Use
          Escherichia Coli
          Computer-Aided Design
          Asparaginase Analogs and Derivatives
          Molecular Structure Evaluation
          Toxicity Tests
          Software
          Drug Stability
          Sequence Analysis
          Mutation
          Antigens
          Allergens
          Lymphoma, B-Cell
          Proteins
      ab: 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 usedsomebioinformatics 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.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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