Title

Molecular docking analysis of a dermatan sulfate tetra-saccharide to human alpha-L-iduronidase

Authors

Darinka P. Durán-Gutiérrez¹, Marisol López-Hidalgo¹, Iliana M. Peña-Gomar², Absalom Zamorano-Carrillo¹, Mónica L. Gómez-Esquivel¹, José L. Castrejón-Flores³ & César A. Reyes-López^1,*

Affiliation

¹Sección de Estudios de Posgrado e Investigación, ENMyH, Instituto Politécnico Nacional, Guillermo Massieu Helguera, No. 239, Fracc. "La Escalera", Ticomán, C.P. 07320, Mexico City, Mexico; ²Departamento de Genética, Hospital IMSS-Bienestar Cuajimalpa, Cuajimalpa de Morelos, Mexico City, Mexico; ³Instituto Politécnico Nacional, Unidad Profesional Interdisciplinaria de Biotecnología, Gustavo A. Madero, Mexico City, Mexico;

Email

Darinka P. Durán-Gutiérrez - E-mail: ddurang1804@alumno.ipn.mx

Marisol López-Hidalgo - E-mail: malopezh@ipn.mx

Iliana M. Peña-Gomar - E-mail: ilemonsepg@gmail.com

Absalom Zamorano-Carrillo - E-mail: azamorano@ipn.mx

Mónica L. Gómez-Esquivel - E-mail: mgomeze@ipn.mx

José L. Castrejón-Flores - E-mail: jlcastrejon@ipn.mx

César A. Reyes-López – E-mail: careyes@ipn.mx

Article Type

Research Article

Date

Received December 1, 2023; Revised December 31, 2023; Accepted December 31, 2023, Published December 31, 2023

Human alpha-L-iduronidase (IDUA) is a 653 amino acid protein involved in the sequential degradation of glycos-amino-glycans (GAG), heparan sulfate (HS), and dermatan sulfate (DS). Some variants in the IDUA gene produce a deficient enzyme that causes un-degraded DS and HS to accumulate in multiple tissues, leading to an organ dysfunction known as muco-poly-saccharidosis type I (MPS I). Molecular and catalytic activity assays of new or rare variants of IDUA do not predict the phenotype that a patient will develop. Therefore, it is of interest to describe the molecular docking analysis, to locate binding regions of DS to IDUA to better understand the effect of a variant on MPS I development. The results presented herein demonstrate the presence of a polar/acidic catalytic site and a basic region in the putative binding site of DS to IDUA. Further, synthetic substrate docking with the enzyme could help in the predictions of the MPS I phenotype.

Keywords

Molecular docking, structures, dermatan sulfate tetrasaccharide, human alpha-L-iduronidase, IDUA, GAG, MPS I

Citation

Durán-Gutiérrez et al. Bioinformation 19(12): 1116-1123 (2023)

Edited by

P Kangueane

ISSN

0973-2063

Publisher

Biomedical Informatics

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.