Identification of L-asparaginases from Streptomyces strains with competitive activity and immunogenic profiles: a bioinformatic approach

PeerJ

article

Iván González-Torres¹  Ernesto Perez-Rueda²  Zahaed Evangelista-Martínez³  Andrés Zárate-Romero¹  Angélica Moreno-Enríquez⁵  Alejandro Huerta-Saquero¹ 

[1] Centro de Nanociencias y Nanotecnología, Universidad Nacional Autónoma de México;Instituto de Matemáticas Aplicadas y Sistemas, Universidad Nacional Autónoma de México;Subsede Sureste;Consejo Nacional de Ciencia y Tecnología;Unidad Genómica Metabólica, Universidad Marista de Mérida

关键词: L-asparaginase;    Acute lymphocytic leukemia;    Streptomyces;    Bioinformatics;   

DOI  :  10.7717/peerj.10276

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

The enzyme L-asparaginase from Escherichia coli is a therapeutic enzyme that has been a cornerstone in the clinical treatment of acute lymphoblastic leukemia for the last decades. However, treatment effectiveness is limited by the highly immunogenic nature of the protein and its cross-reactivity towards L-glutamine. In this work, a bioinformatic approach was used to identify, select and computationally characterize L-asparaginases from Streptomyces through sequence-based screening analyses, immunoinformatics, homology modeling, and molecular docking studies. Based on its predicted low immunogenicity and excellent enzymatic activity, we selected a previously uncharacterized L-asparaginase from Streptomyces scabrisporus. Furthermore, two putative asparaginase binding sites were identified and a 3D model is proposed. These promising features allow us to propose L-asparaginase from S. scabrisporus as an alternative for the treatment of acute lymphocytic leukemia.

【 授权许可】

CC BY