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Preliminary Study of Structural Changes of Glucose-6-Phosphate Dehydrogenase Deficiency Variants

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency disorder affecting over 400 million individuals worldwide. G6PD protects red blood cells (RBC) from the harmful effects of oxidative substances. There are more than 400 G6PD mutations, of which 186 variants have...

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Autores principales: Louis, Naveen E., Hamza, Muaawia A., Baharuddin, Puteri NSD Engku Baharuddin, Chandran, Shamini, Latif, Nurriza A., Alonazi, Mona A., Halim, Khairul B.A., Warsy, Arjumand, Amran, Syazwani I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: China Medical University 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9629405/
https://www.ncbi.nlm.nih.gov/pubmed/36381187
http://dx.doi.org/10.37796/2211-8039.1355
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author Louis, Naveen E.
Hamza, Muaawia A.
Baharuddin, Puteri NSD Engku Baharuddin
Chandran, Shamini
Latif, Nurriza A.
Alonazi, Mona A.
Halim, Khairul B.A.
Warsy, Arjumand
Amran, Syazwani I.
author_facet Louis, Naveen E.
Hamza, Muaawia A.
Baharuddin, Puteri NSD Engku Baharuddin
Chandran, Shamini
Latif, Nurriza A.
Alonazi, Mona A.
Halim, Khairul B.A.
Warsy, Arjumand
Amran, Syazwani I.
author_sort Louis, Naveen E.
collection PubMed
description Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency disorder affecting over 400 million individuals worldwide. G6PD protects red blood cells (RBC) from the harmful effects of oxidative substances. There are more than 400 G6PD mutations, of which 186 variants have shown to be linked to G6PD deficiency by decreasing the activity or stability of the enzyme. Different variants manifest different clinical phenotypes which complicate comprehending the mechanism of the disease. In order to carry out computational approaches to elucidate the structural changes of different G6PD variants that are common to the Asian population, a complete G6PD monomer-ligand complex was constructed using AutoDock 4.2, and the molecular dynamics simulation package GROMACS 4.6.7 was used to study the protein dynamics. The G410D and V291M variants were chosen to represent classes I and II respectively and were created by in silico site-directed mutagenesis. Results from the Root mean square deviation (RMSD), Root mean square fluctuation (RMSF) and Radius of gyration (Rg) analyses provided insights on the structure – function relationship for the variants. G410D indicated impaired dimerization and structural NADP binding while the impaired catalytic activity for V291M was indicated by a conformational change at its mutation site.
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spelling pubmed-96294052022-11-14 Preliminary Study of Structural Changes of Glucose-6-Phosphate Dehydrogenase Deficiency Variants Louis, Naveen E. Hamza, Muaawia A. Baharuddin, Puteri NSD Engku Baharuddin Chandran, Shamini Latif, Nurriza A. Alonazi, Mona A. Halim, Khairul B.A. Warsy, Arjumand Amran, Syazwani I. Biomedicine (Taipei) Original Article Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency disorder affecting over 400 million individuals worldwide. G6PD protects red blood cells (RBC) from the harmful effects of oxidative substances. There are more than 400 G6PD mutations, of which 186 variants have shown to be linked to G6PD deficiency by decreasing the activity or stability of the enzyme. Different variants manifest different clinical phenotypes which complicate comprehending the mechanism of the disease. In order to carry out computational approaches to elucidate the structural changes of different G6PD variants that are common to the Asian population, a complete G6PD monomer-ligand complex was constructed using AutoDock 4.2, and the molecular dynamics simulation package GROMACS 4.6.7 was used to study the protein dynamics. The G410D and V291M variants were chosen to represent classes I and II respectively and were created by in silico site-directed mutagenesis. Results from the Root mean square deviation (RMSD), Root mean square fluctuation (RMSF) and Radius of gyration (Rg) analyses provided insights on the structure – function relationship for the variants. G410D indicated impaired dimerization and structural NADP binding while the impaired catalytic activity for V291M was indicated by a conformational change at its mutation site. China Medical University 2022-09-01 /pmc/articles/PMC9629405/ /pubmed/36381187 http://dx.doi.org/10.37796/2211-8039.1355 Text en © the Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Original Article
Louis, Naveen E.
Hamza, Muaawia A.
Baharuddin, Puteri NSD Engku Baharuddin
Chandran, Shamini
Latif, Nurriza A.
Alonazi, Mona A.
Halim, Khairul B.A.
Warsy, Arjumand
Amran, Syazwani I.
Preliminary Study of Structural Changes of Glucose-6-Phosphate Dehydrogenase Deficiency Variants
title Preliminary Study of Structural Changes of Glucose-6-Phosphate Dehydrogenase Deficiency Variants
title_full Preliminary Study of Structural Changes of Glucose-6-Phosphate Dehydrogenase Deficiency Variants
title_fullStr Preliminary Study of Structural Changes of Glucose-6-Phosphate Dehydrogenase Deficiency Variants
title_full_unstemmed Preliminary Study of Structural Changes of Glucose-6-Phosphate Dehydrogenase Deficiency Variants
title_short Preliminary Study of Structural Changes of Glucose-6-Phosphate Dehydrogenase Deficiency Variants
title_sort preliminary study of structural changes of glucose-6-phosphate dehydrogenase deficiency variants
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9629405/
https://www.ncbi.nlm.nih.gov/pubmed/36381187
http://dx.doi.org/10.37796/2211-8039.1355
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