Rhizobium etli asparaginase II: an alternative for acute lymphoblastic leukemia (ALL) treatment.

Abstract:

:Bacterial L-asparaginase has been a universal component of therapies for childhood acute lymphoblastic leukemia since the 1970s. Two principal enzymes derived from Escherichia coli and Erwinia chrysanthemi are the only options clinically approved to date. We recently reported a study of recombinant L-asparaginase (AnsA) from Rhizobium etli and described an increasing type of AnsA family members. Sequence analysis revealed four conserved motifs with notable differences with respect to the conserved regions of amino acid sequences of type I and type II L-asparaginases, particularly in comparison with therapeutic enzymes from E. coli and E. chrysanthemi. These differences suggested a distinct immunological specificity. Here, we report an in silico analysis that revealed immunogenic determinants of AnsA. Also, we used an extensive approach to compare the crystal structures of E. coli and E. chrysantemi asparaginases with a computational model of AnsA and identified immunogenic epitopes. A three-dimensional model of AsnA revealed, as expected based on sequence dissimilarities, completely different folding and different immunogenic epitopes. This approach could be very useful in transcending the problem of immunogenicity in two major ways: by chemical modifications of epitopes to reduce drug immunogenicity, and by site-directed mutagenesis of amino acid residues to diminish immunogenicity without reduction of enzymatic activity.

journal_name

Bioengineered

journal_title

Bioengineered

authors

Huerta-Saquero A,Evangelista-Martínez Z,Moreno-Enriquez A,Perez-Rueda E

doi

10.4161/bioe.21710

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

30-6

issue

1

eissn

2165-5979

issn

2165-5987

pii

21710

journal_volume

4

pub_type

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