The FAD synthetase from the human pathogen Streptococcus pneumoniae: a bifunctional enzyme exhibiting activity-dependent redox requirements

Abstract Prokaryotic bifunctional FAD synthetases (FADSs) catalyze the biosynthesis of FMN and FAD, whereas in eukaryotes two enzymes are required for the same purpose. FMN and FAD are key cofactors to maintain the flavoproteome homeostasis in all type of organisms. Here we shed light to the propert...

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Autores principales:	María Sebastián, Erandi Lira-Navarrete, Ana Serrano, Carlos Marcuello, Adrián Velázquez-Campoy, Anabel Lostao, Ramón Hurtado-Guerrero, Milagros Medina, Marta Martínez-Júlvez
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d4edd25e669b41d59c704c9da5d7440d
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spelling	oai:doaj.org-article:d4edd25e669b41d59c704c9da5d7440d2021-12-02T12:32:43ZThe FAD synthetase from the human pathogen Streptococcus pneumoniae: a bifunctional enzyme exhibiting activity-dependent redox requirements10.1038/s41598-017-07716-52045-2322https://doaj.org/article/d4edd25e669b41d59c704c9da5d7440d2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07716-5https://doaj.org/toc/2045-2322Abstract Prokaryotic bifunctional FAD synthetases (FADSs) catalyze the biosynthesis of FMN and FAD, whereas in eukaryotes two enzymes are required for the same purpose. FMN and FAD are key cofactors to maintain the flavoproteome homeostasis in all type of organisms. Here we shed light to the properties of the hitherto unstudied bacterial FADS from the human pathogen Streptococcus pneumoniae (SpnFADS). As other members of the family, SpnFADS catalyzes the three typical activities of prokaryotic FADSs: riboflavin kinase (RFK), ATP:FMN:adenylyltransferase (FMNAT), and FAD pyrophosphorylase (FADpp). However, several SpnFADS biophysical properties differ from those of other family members. In particular; i) the RFK activity is not inhibited by the riboflavin (RF) substrate, ii) the FMNAT and FADSpp activities require flavin substrates in the reduced state, iii) binding of adenine nucleotide ligands is required for the binding of flavinic substrates/products and iv) the monomer is the preferred state. Collectively, our results add interesting mechanistic differences among the few prokaryotic bifunctional FADSs already characterized, which might reflect the adaptation of the enzyme to relatively different environments. In a health point of view, differences among FADS family members provide us with a framework to design selective compounds targeting these enzymes for the treatment of diverse infectious diseases.María SebastiánErandi Lira-NavarreteAna SerranoCarlos MarcuelloAdrián Velázquez-CampoyAnabel LostaoRamón Hurtado-GuerreroMilagros MedinaMarta Martínez-JúlvezNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q María Sebastián Erandi Lira-Navarrete Ana Serrano Carlos Marcuello Adrián Velázquez-Campoy Anabel Lostao Ramón Hurtado-Guerrero Milagros Medina Marta Martínez-Júlvez The FAD synthetase from the human pathogen Streptococcus pneumoniae: a bifunctional enzyme exhibiting activity-dependent redox requirements
description	Abstract Prokaryotic bifunctional FAD synthetases (FADSs) catalyze the biosynthesis of FMN and FAD, whereas in eukaryotes two enzymes are required for the same purpose. FMN and FAD are key cofactors to maintain the flavoproteome homeostasis in all type of organisms. Here we shed light to the properties of the hitherto unstudied bacterial FADS from the human pathogen Streptococcus pneumoniae (SpnFADS). As other members of the family, SpnFADS catalyzes the three typical activities of prokaryotic FADSs: riboflavin kinase (RFK), ATP:FMN:adenylyltransferase (FMNAT), and FAD pyrophosphorylase (FADpp). However, several SpnFADS biophysical properties differ from those of other family members. In particular; i) the RFK activity is not inhibited by the riboflavin (RF) substrate, ii) the FMNAT and FADSpp activities require flavin substrates in the reduced state, iii) binding of adenine nucleotide ligands is required for the binding of flavinic substrates/products and iv) the monomer is the preferred state. Collectively, our results add interesting mechanistic differences among the few prokaryotic bifunctional FADSs already characterized, which might reflect the adaptation of the enzyme to relatively different environments. In a health point of view, differences among FADS family members provide us with a framework to design selective compounds targeting these enzymes for the treatment of diverse infectious diseases.
format	article
author	María Sebastián Erandi Lira-Navarrete Ana Serrano Carlos Marcuello Adrián Velázquez-Campoy Anabel Lostao Ramón Hurtado-Guerrero Milagros Medina Marta Martínez-Júlvez
author_facet	María Sebastián Erandi Lira-Navarrete Ana Serrano Carlos Marcuello Adrián Velázquez-Campoy Anabel Lostao Ramón Hurtado-Guerrero Milagros Medina Marta Martínez-Júlvez
author_sort	María Sebastián
title	The FAD synthetase from the human pathogen Streptococcus pneumoniae: a bifunctional enzyme exhibiting activity-dependent redox requirements
title_short	The FAD synthetase from the human pathogen Streptococcus pneumoniae: a bifunctional enzyme exhibiting activity-dependent redox requirements
title_full	The FAD synthetase from the human pathogen Streptococcus pneumoniae: a bifunctional enzyme exhibiting activity-dependent redox requirements
title_fullStr	The FAD synthetase from the human pathogen Streptococcus pneumoniae: a bifunctional enzyme exhibiting activity-dependent redox requirements
title_full_unstemmed	The FAD synthetase from the human pathogen Streptococcus pneumoniae: a bifunctional enzyme exhibiting activity-dependent redox requirements
title_sort	fad synthetase from the human pathogen streptococcus pneumoniae: a bifunctional enzyme exhibiting activity-dependent redox requirements
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d4edd25e669b41d59c704c9da5d7440d
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The FAD synthetase from the human pathogen Streptococcus pneumoniae: a bifunctional enzyme exhibiting activity-dependent redox requirements

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