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Reference: Boonyuen, U, Chamchoy, K, Swangsri, T et al., (2017). A trade off between catalytic activity and protein stability determines the clinical manifestations of glucose-6-phosphate dehydrogenase (G6PD) deficiency. International Journal of Biological Macromolecules, 104 (Pt A), 145-156.Citable link to this page:

 

A trade off between catalytic activity and protein stability determines the clinical manifestations of glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Abstract: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common polymorphism and enzymopathy in humans, affecting approximately 400 million people worldwide. It is responsible for various clinical manifestations, including favism, hemolytic anemia, chronic non-spherocytic hemolytic anemia, spontaneous abortion, and neonatal hyperbilirubinemia. Understanding the molecular mechanisms underlying the severity of G6PD deficiency is of great importance but that of many G6PD variants are still unknown. In this study, we report the construction, expression, purification, and biochemical characterization in terms of kinetic properties and stability of five clinical G6PD variants-G6PD Bangkok, G6PD Bangkok noi, G6PD Songklanagarind, G6PD Canton+Bangkok noi, and G6PD Union+Viangchan. G6PD Bangkok and G6PD Canton+Bangkok noi showed a complete loss of catalytic activity and moderate reduction in thermal stability when compared with the native G6PD. G6PD Bangkok noi and G6PD Union+Viangchan showed a significant reduction in catalytic efficiency, whereas G6PD Songklanagarind showed a catalytic activity comparable to the wild-type enzyme. The Union+Viangchan mutation showed a remarkable effect on the global stability of the enzyme. In addition, our results indicate that the location of mutations in G6PD variants affects their catalytic activity, stability, and structure. Hence, our results provide a molecular explanation for clinical manifestations observed in individuals with G6PD deficiency.

Publication status:PublishedPeer Review status:Peer reviewedVersion:Publisher's versionDate of acceptance:2017-06-01 Funder: Wellcome Trust   Funder: Thailand Research Fund   Notes:© 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license(http://creativecommons.org/licenses/by/4.0/).

Bibliographic Details

Publisher: Elsevier

Publisher Website: http://www.elsevier.com/

Journal: International Journal of Biological Macromoleculessee more from them

Publication Website: http://www.sciencedirect.com/science/journal/01418130

Volume: 104

Issue: Pt A

Issue Date: 2017-06

pages:145-156Identifiers

Doi: https://doi.org/10.1016/j.ijbiomac.2017.06.002

Eissn: 1879-0003

Issn: 0141-8130

Uuid: uuid:f33e9a91-39aa-46dc-ae56-4e626922392a

Urn: uri:f33e9a91-39aa-46dc-ae56-4e626922392a

Pubs-id: pubs:700588 Item Description

Type: journal-article;

Language: eng

Version: Publisher's versionKeywords: Catalytic activity G6PD deficiency Thermal stability

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Autor: Boonyuen, U - - - Chamchoy, K - - - Swangsri, T - - - Junkree, T - - - Day, NPJ - Oxford, MSD, NDM, Tropical Medicine - - - White

Fuente: https://ora.ox.ac.uk/objects/uuid:f33e9a91-39aa-46dc-ae56-4e626922392a



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