117191 20220617170936.0 doi 10.1096/fj.202000566r sideral 118903 ART-2020-118903 eng Anoz-Carbonell, Ernesto Universidad de Zaragoza (orcid)0000-0002-6649-9153 Human riboflavin kinase: Species-specific traits in the biosynthesis of the FMN cofactor 2020 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. Access copy available to the general public Unrestricted 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 info:eu-repo/semantics/openAccess by-nc-nd http://creativecommons.org/licenses/by-nc-nd/3.0/es/ 5.191 2020 BIOLOGY 14 / 93 = 0.151 2020 Q1 T1 CELL BIOLOGY 77 / 195 = 0.395 2020 Q2 T2 BIOCHEMISTRY & MOLECULAR BIOLOGY 84 / 297 = 0.283 2020 Q2 T1 1.709 2020 Biochemistry 2020 Q1 Biotechnology 2020 Q1 Molecular Biology 2020 Q1 Medicine (miscellaneous) 2020 Q1 Genetics 2020 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Rivero, Maribel Polo, Victor Universidad de Zaragoza (orcid)0000-0001-5823-7965 Velázquez-Campoy, Adrián Universidad de Zaragoza (orcid)0000-0001-5702-4538 Medina, Milagros Universidad de Zaragoza (orcid)0000-0001-8743-0182 2012 755 Universidad de Zaragoza Dpto. Química Física Área Química Física 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 34, 8 (2020), 10871-10886 FASEB j. The FASEB Journal 0892-6638 1546014 http://zaguan.unizar.es/record/117191/files/texto_completo.pdf Versión publicada 2425556 http://zaguan.unizar.es/record/117191/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:117191 articulos driver 2022-06-17-14:31:34 ARTICLE