Polyamine-Based Thiols in Trypanosomatids : evolution, protein structural adaptations and biological functions

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Polyamine-Based Thiols in Trypanosomatids : evolution, protein structural adaptations and biological functions

Tema

PARASITOS
LEISHMANIASIS
POLIAMINA
BIBLIOGRAFIA NACIONAL QUIMICA
2018

Abstract

Significance: Major pathogenic enterobacteria and protozoan parasites from the phylum Euglenozoa, such as trypanosomatids, are endowed with glutathione (GSH)-spermidine (Sp) derivatives that play important roles in signaling and metal and thiol-redox homeostasis. For some Euglenozoa lineages, the GSH-Sp conjugates represent the main redox cosubstrates around which entire new redox systems have evolved. Several proteins underwent molecular adaptations to synthesize and utilize the new polyamine-based thiols. Recent Advances: The genomes of closely related organisms have recently been sequenced, which allows mining and analysis of gene sequences that belong to these peculiar redox systems. Similarly, the three-dimensional structures of several of these proteins have been solved, which allows for comparison with their counterparts in classical redox systems that rely on GSH/glutaredoxin and thioredoxin. Critical Issues: The evolutionary and structural aspects related to the emergence and use of GSH-Sp conjugates in Euglenozoa are reviewed focusing on unique structural specializations that proteins developed to use N1,N8-bisglutathionylspermidine (trypanothione) as redox cosubstrate. An updated overview on the biochemical and biological significance of the major enzymatic activities is also provided. Future Directions: A thiol-redox system strictly dependent on trypanothione is a feature unique to trypanosomatids. The physicochemical properties of the polyamine-GSH conjugates were a major driving force for structural adaptation of proteins that use these thiols as ligand and redox cofactor. In fact, the structural differences of indispensable components of this system can be exploited toward selective drug development. Future research should clarify whether additional cellular processes are regulated by the trypanothione system. Antioxid. Redox Signal. 28, 463–486.

Autor

Manta, Bruno.
Bonilla, Mariana.
Fiestas, Lucía
Sturlese, Mattia
Bellanda, Massimo
Comini, Marcelo A

Fuente

Antioxidants and Redox Signaling v. 28, no. 6, 2018. -- p. 463-486

Editor

Mary Ann Liebert, Inc

Fecha

2018

Derechos

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Artículo

Identificador

DOI: 10.1089/ars.2017.7133

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PDF
Fecha de agregación
November 9, 2018
Colección
Bibliografía Nacional Química
Tipo de Elemento
Document
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Citación
Manta, Bruno., “Polyamine-Based Thiols in Trypanosomatids : evolution, protein structural adaptations and biological functions,” RIQUIM - Repositorio Institucional de la Facultad de Química - UdelaR, accessed November 18, 2018, http://riquim.fq.edu.uy/items/show/5358.
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