Bioinformatic Analysis of the Human Recombinant Iduronate 2-Sulfate Sulfatase



Edwin D. Morales-Álvarez1, 2, , Claudia M. Rivera-Hoyos1, 3, , Patricia Landázuri1, *, Raúl A. Poutou-Piñales3, Aura M. Pedroza-Rodríguez4
1 Research Group on Cardiovascular and Metabolic Diseases (GECAVYME), Faculty of Health Sciences, University of Quindio, Armenia-Quindío, Colombia, South America
2 Department of Chemistry, Research Group on Genetics, Biodiversity and Ecosystem Management (GEBIOME), Faculty of Exact and Natural Sciences, University of Caldas, Manizales-Caldas, Colombia, South America
3 Laboratory of Molecular Biotechnology, Group of Environmental and Industrial Biotechnology (GBAI), Department of Microbiology, Faculty of Sciences, Pontificia Universidad Javeriana, Bogotá, D.C. Colombia, South America
4 Laboratory of Environmental and Soil Microbiology, Group of Environmental and Industrial Biotechnology (GBAI), Department of Microbiology, Faculty of Sciences, Pontificia Universidad Javeriana, Bogotá, D.C. Colombia, South America


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© Morales-Álvarez et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Research Group on Cardiovascular and Metabolic Diseases (GECAVYME), Faculty of Health Sciences, University of Quindio, Armenia-Quindío, Colombia, South America; Fax: (57-6)7359305; E-mail: plandazu@uniquindio.edu.co Both authors contributed equally in this study.


Abstract

Mucopolysaccharidosis type II is a human recessive disease linked to the X chromosome caused by deficiency of lysosomal enzyme Iduronate 2-Sulfate Sulfatase (IDS), which leads to accumulation of glycosaminoglycans in tissues and organs. The human enzyme has been expressed in Escherichia coli and Pichia pastoris in attempt to develop more successful expression systems that allow the production of recombinant IDS for Enzyme Replacement Therapy (ERT). However, the preservation of native signal peptide in the sequence has caused conflicts in processing and recognition in the past, which led to problems in expression and enzyme activity. With the main object being the improvement of the expression system, we eliminate the native signal peptide of human recombinant IDS. The resulting sequence showed two modified codons, thus, our study aimed to analyze computationally the nucleotide sequence of the IDSnh without signal peptide in order to determine the 3D structure and other biochemical properties to compare them with the native human IDS (IDSnh). Results showed that there are no significant differences between both molecules in spite of the two-codon modifications detected in the recombinant DNA sequence.

Keywords: Bioinformatics, hunter syndrome, iduronate 2-sulfate sulfatase, native signal peptide, three dimensional protein structure.