Human riboflavin kinase: Species-specific traits in the biosynthesis of the FMN cofactor

Human riboflavin kinase (HsRFK) catalyzes vitamin B<inf>2</inf> (riboflavin) phosphorylation to flavin mononucleotide (FMN), obligatory step in flavin cofactor synthesis. HsRFK expression is related to protection from oxidative stress, amyloid-β toxicity, and some malignant cancers prog...

Descripción completa

Detalles Bibliográficos
Autores: Anoz-Carbonell, Ernesto, Rivero, Maribel, Polo, Victor, Velázquez-Campoy, Adrián, Medina, Milagros
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universidad de Zaragoza
Repositorio:Zaguán. Repositorio Digital de la Universidad de Zaragoza
OAI Identifier:oai:zaguan.unizar.es:117191
Acceso en línea:http://zaguan.unizar.es/record/117191
Access Level:acceso abierto
id ES_c0d6c3abe2f1624b9be830ffde063cb2
oai_identifier_str oai:zaguan.unizar.es:117191
network_acronym_str ES
network_name_str España
repository_id_str
spelling Human riboflavin kinase: Species-specific traits in the biosynthesis of the FMN cofactorAnoz-Carbonell, ErnestoRivero, MaribelPolo, VictorVelázquez-Campoy, AdriánMedina, MilagrosHuman riboflavin kinase (HsRFK) catalyzes vitamin B<inf>2</inf> (riboflavin) phosphorylation to flavin mononucleotide (FMN), obligatory step in flavin cofactor synthesis. HsRFK expression is related to protection from oxidative stress, amyloid-β toxicity, and some malignant cancers progression. Its downregulation alters expression profiles of clock-controlled metabolic-genes and destroys flavins protection on stroke treatments, while its activity reduction links to protein-energy malnutrition and thyroid hormones decrease. We explored specific features of the mechanisms underlying the regulation of HsRFK activity, showing that both reaction products regulate it through competitive inhibition. Fast-kinetic studies show that despite HsRFK binds faster and preferably the reaction substrates, the complex holding both products is kinetically most stable. An intricate ligand binding landscape with all combinations of substrates/products competing with the catalytic complex and exhibiting moderate cooperativity is also presented. These data might contribute to better understanding the molecular bases of pathologies coursing with aberrant HsRFK availability, and envisage that interaction with its client-apoproteins might favor FMN release. Finally, HsRFK parameters differ from those of the so far evaluated bacterial counterparts, reinforcing the idea of species-specific mechanisms in RFK catalysis. These observations support HsRFK as potential therapeutic target because of its key functions, while also envisage bacterial RFK modules as potential antimicrobial targets.2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://zaguan.unizar.es/record/117191reponame:Zaguán. Repositorio Digital de la Universidad de Zaragozainstname:Universidad de ZaragozaInglésinfo:eu-repo/grantAgreement/ES/DGA-FEDER/E35-20Rinfo:eu-repo/grantAgreement/ES/MICINN-AEI/PID2019-103901GB-I00info:eu-repo/grantAgreement/ES/MINECO-AEI-FEDER/BIO2016-75183-Pinfo:eu-repo/semantics/openAccessoai:zaguan.unizar.es:1171912026-05-29T13:59:51Z
dc.title.none.fl_str_mv Human riboflavin kinase: Species-specific traits in the biosynthesis of the FMN cofactor
title Human riboflavin kinase: Species-specific traits in the biosynthesis of the FMN cofactor
spellingShingle Human riboflavin kinase: Species-specific traits in the biosynthesis of the FMN cofactor
Anoz-Carbonell, Ernesto
title_short Human riboflavin kinase: Species-specific traits in the biosynthesis of the FMN cofactor
title_full Human riboflavin kinase: Species-specific traits in the biosynthesis of the FMN cofactor
title_fullStr Human riboflavin kinase: Species-specific traits in the biosynthesis of the FMN cofactor
title_full_unstemmed Human riboflavin kinase: Species-specific traits in the biosynthesis of the FMN cofactor
title_sort Human riboflavin kinase: Species-specific traits in the biosynthesis of the FMN cofactor
dc.creator.none.fl_str_mv Anoz-Carbonell, Ernesto
Rivero, Maribel
Polo, Victor
Velázquez-Campoy, Adrián
Medina, Milagros
author Anoz-Carbonell, Ernesto
author_facet Anoz-Carbonell, Ernesto
Rivero, Maribel
Polo, Victor
Velázquez-Campoy, Adrián
Medina, Milagros
author_role author
author2 Rivero, Maribel
Polo, Victor
Velázquez-Campoy, Adrián
Medina, Milagros
author2_role author
author
author
author
description Human riboflavin kinase (HsRFK) catalyzes vitamin B<inf>2</inf> (riboflavin) phosphorylation to flavin mononucleotide (FMN), obligatory step in flavin cofactor synthesis. HsRFK expression is related to protection from oxidative stress, amyloid-β toxicity, and some malignant cancers progression. Its downregulation alters expression profiles of clock-controlled metabolic-genes and destroys flavins protection on stroke treatments, while its activity reduction links to protein-energy malnutrition and thyroid hormones decrease. We explored specific features of the mechanisms underlying the regulation of HsRFK activity, showing that both reaction products regulate it through competitive inhibition. Fast-kinetic studies show that despite HsRFK binds faster and preferably the reaction substrates, the complex holding both products is kinetically most stable. An intricate ligand binding landscape with all combinations of substrates/products competing with the catalytic complex and exhibiting moderate cooperativity is also presented. These data might contribute to better understanding the molecular bases of pathologies coursing with aberrant HsRFK availability, and envisage that interaction with its client-apoproteins might favor FMN release. Finally, HsRFK parameters differ from those of the so far evaluated bacterial counterparts, reinforcing the idea of species-specific mechanisms in RFK catalysis. These observations support HsRFK as potential therapeutic target because of its key functions, while also envisage bacterial RFK modules as potential antimicrobial targets.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://zaguan.unizar.es/record/117191
url http://zaguan.unizar.es/record/117191
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/ES/DGA-FEDER/E35-20R
info:eu-repo/grantAgreement/ES/MICINN-AEI/PID2019-103901GB-I00
info:eu-repo/grantAgreement/ES/MINECO-AEI-FEDER/BIO2016-75183-P
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv
publisher.none.fl_str_mv
dc.source.none.fl_str_mv reponame:Zaguán. Repositorio Digital de la Universidad de Zaragoza
instname:Universidad de Zaragoza
instname_str Universidad de Zaragoza
reponame_str Zaguán. Repositorio Digital de la Universidad de Zaragoza
collection Zaguán. Repositorio Digital de la Universidad de Zaragoza
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869418510974713856
score 15,300719

Similares en LA Referencia