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Published on: March 22, 2012
Identification of L-asparaginases from Streptomyces strains with competitive activity and immunogenic profiles: a
Iván González-Torres1, Ernesto Perez-Rueda2, Zahaed Evangelista-Martínez3
1Centro de Nanociencias y Nanotecnología, Universidad Nacional Autónoma de México, Ensenada, Baja California, México.
Abstract:
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.

