Comparison of carbohydrate ABC importers from Mycobacterium tuberculosis

Abstract Background Mycobacterium tuberculosis, the etiological agent of tuberculosis, has at least four ATP-Binding Cassette (ABC) transporters dedicated to carbohydrate uptake: LpqY/SugABC, UspABC, Rv2038c-41c, and UgpAEBC. LpqY/SugABC transporter is essential for M. tuberculosis survival in vivo...

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Autores principales:	Lilia I. De la Torre, José G. Vergara Meza, Sindy Cabarca, André G. Costa-Martins, Andrea Balan
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Carbohydrate uptake ABC transporters Phylogeny Multitask NBDs Structure-function Protein-protein interaction Biotechnology TP248.13-248.65 Genetics QH426-470
Acceso en línea:	https://doaj.org/article/cf0411f58d674ecba1badff051aaa41a
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spelling	oai:doaj.org-article:cf0411f58d674ecba1badff051aaa41a2021-11-21T12:26:32ZComparison of carbohydrate ABC importers from Mycobacterium tuberculosis10.1186/s12864-021-07972-w1471-2164https://doaj.org/article/cf0411f58d674ecba1badff051aaa41a2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12864-021-07972-whttps://doaj.org/toc/1471-2164Abstract Background Mycobacterium tuberculosis, the etiological agent of tuberculosis, has at least four ATP-Binding Cassette (ABC) transporters dedicated to carbohydrate uptake: LpqY/SugABC, UspABC, Rv2038c-41c, and UgpAEBC. LpqY/SugABC transporter is essential for M. tuberculosis survival in vivo and potentially involved in the recycling of cell wall components. The three-dimensional structures of substrate-binding proteins (SBPs) LpqY, UspC, and UgpB were described, however, questions about how these proteins interact with the cognate transporter are still being explored. Components of these transporters, such as SBPs, show high immunogenicity and could be used for the development of diagnostic and therapeutic tools. In this work, we used a phylogenetic and structural bioinformatics approach to compare the four systems, in an attempt to predict functionally important regions. Results Through the analysis of the putative orthologs of the carbohydrate ABC importers in species of Mycobacterium genus it was shown that Rv2038c-41c and UgpAEBC systems are restricted to pathogenic species. We showed that the components of the four ABC importers are phylogenetically separated into four groups defined by structural differences in regions that modulate the functional activity or the interaction with domain partners. The regulatory region in nucleotide-binding domains, the periplasmic interface in transmembrane domains and the ligand-binding pocket of the substrate-binding proteins define their substrates and segregation in different branches. The interface between transmembrane domains and nucleotide-binding domains show conservation of residues and charge. Conclusions The presence of four ABC transporters in M. tuberculosis dedicated to uptake and transport of different carbohydrate sources, and the exclusivity of at least two of them being present only in pathogenic species of Mycobacterium genus, highlights their relevance in virulence and pathogenesis. The significant differences in the SBPs, not present in eukaryotes, and in the regulatory region of NBDs can be explored for the development of inhibitory drugs targeting the bacillus. The possible promiscuity of NBDs also contributes to a less specific and more comprehensive control approach.Lilia I. De la TorreJosé G. Vergara MezaSindy CabarcaAndré G. Costa-MartinsAndrea BalanBMCarticleCarbohydrate uptakeABC transportersPhylogenyMultitask NBDsStructure-functionProtein-protein interactionBiotechnologyTP248.13-248.65GeneticsQH426-470ENBMC Genomics, Vol 22, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Carbohydrate uptake ABC transporters Phylogeny Multitask NBDs Structure-function Protein-protein interaction Biotechnology TP248.13-248.65 Genetics QH426-470
spellingShingle	Carbohydrate uptake ABC transporters Phylogeny Multitask NBDs Structure-function Protein-protein interaction Biotechnology TP248.13-248.65 Genetics QH426-470 Lilia I. De la Torre José G. Vergara Meza Sindy Cabarca André G. Costa-Martins Andrea Balan Comparison of carbohydrate ABC importers from Mycobacterium tuberculosis
description	Abstract Background Mycobacterium tuberculosis, the etiological agent of tuberculosis, has at least four ATP-Binding Cassette (ABC) transporters dedicated to carbohydrate uptake: LpqY/SugABC, UspABC, Rv2038c-41c, and UgpAEBC. LpqY/SugABC transporter is essential for M. tuberculosis survival in vivo and potentially involved in the recycling of cell wall components. The three-dimensional structures of substrate-binding proteins (SBPs) LpqY, UspC, and UgpB were described, however, questions about how these proteins interact with the cognate transporter are still being explored. Components of these transporters, such as SBPs, show high immunogenicity and could be used for the development of diagnostic and therapeutic tools. In this work, we used a phylogenetic and structural bioinformatics approach to compare the four systems, in an attempt to predict functionally important regions. Results Through the analysis of the putative orthologs of the carbohydrate ABC importers in species of Mycobacterium genus it was shown that Rv2038c-41c and UgpAEBC systems are restricted to pathogenic species. We showed that the components of the four ABC importers are phylogenetically separated into four groups defined by structural differences in regions that modulate the functional activity or the interaction with domain partners. The regulatory region in nucleotide-binding domains, the periplasmic interface in transmembrane domains and the ligand-binding pocket of the substrate-binding proteins define their substrates and segregation in different branches. The interface between transmembrane domains and nucleotide-binding domains show conservation of residues and charge. Conclusions The presence of four ABC transporters in M. tuberculosis dedicated to uptake and transport of different carbohydrate sources, and the exclusivity of at least two of them being present only in pathogenic species of Mycobacterium genus, highlights their relevance in virulence and pathogenesis. The significant differences in the SBPs, not present in eukaryotes, and in the regulatory region of NBDs can be explored for the development of inhibitory drugs targeting the bacillus. The possible promiscuity of NBDs also contributes to a less specific and more comprehensive control approach.
format	article
author	Lilia I. De la Torre José G. Vergara Meza Sindy Cabarca André G. Costa-Martins Andrea Balan
author_facet	Lilia I. De la Torre José G. Vergara Meza Sindy Cabarca André G. Costa-Martins Andrea Balan
author_sort	Lilia I. De la Torre
title	Comparison of carbohydrate ABC importers from Mycobacterium tuberculosis
title_short	Comparison of carbohydrate ABC importers from Mycobacterium tuberculosis
title_full	Comparison of carbohydrate ABC importers from Mycobacterium tuberculosis
title_fullStr	Comparison of carbohydrate ABC importers from Mycobacterium tuberculosis
title_full_unstemmed	Comparison of carbohydrate ABC importers from Mycobacterium tuberculosis
title_sort	comparison of carbohydrate abc importers from mycobacterium tuberculosis
publisher	BMC
publishDate	2021
url	https://doaj.org/article/cf0411f58d674ecba1badff051aaa41a
work_keys_str_mv	AT liliaidelatorre comparisonofcarbohydrateabcimportersfrommycobacteriumtuberculosis AT josegvergarameza comparisonofcarbohydrateabcimportersfrommycobacteriumtuberculosis AT sindycabarca comparisonofcarbohydrateabcimportersfrommycobacteriumtuberculosis AT andregcostamartins comparisonofcarbohydrateabcimportersfrommycobacteriumtuberculosis AT andreabalan comparisonofcarbohydrateabcimportersfrommycobacteriumtuberculosis
_version_	1718419032749637632

Comparison of carbohydrate ABC importers from Mycobacterium tuberculosis

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