000117191 001__ 117191
000117191 005__ 20220617170936.0
000117191 0247_ $$2doi$$a10.1096/fj.202000566r
000117191 0248_ $$2sideral$$a118903
000117191 037__ $$aART-2020-118903
000117191 041__ $$aeng
000117191 100__ $$0(orcid)0000-0002-6649-9153$$aAnoz-Carbonell, Ernesto$$uUniversidad de Zaragoza
000117191 245__ $$aHuman riboflavin kinase: Species-specific traits in the biosynthesis of the FMN cofactor
000117191 260__ $$c2020
000117191 5060_ $$aAccess copy available to the general public$$fUnrestricted
000117191 5203_ $$aHuman 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.
000117191 536__ $$9info:eu-repo/grantAgreement/ES/DGA-FEDER/E35-20R$$9info:eu-repo/grantAgreement/ES/MICINN-AEI/PID2019-103901GB-I00$$9info:eu-repo/grantAgreement/ES/MINECO-AEI-FEDER/BIO2016-75183-P
000117191 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000117191 590__ $$a5.191$$b2020
000117191 591__ $$aBIOLOGY$$b14 / 93 = 0.151$$c2020$$dQ1$$eT1
000117191 591__ $$aCELL BIOLOGY$$b77 / 195 = 0.395$$c2020$$dQ2$$eT2
000117191 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b84 / 297 = 0.283$$c2020$$dQ2$$eT1
000117191 592__ $$a1.709$$b2020
000117191 593__ $$aBiochemistry$$c2020$$dQ1
000117191 593__ $$aBiotechnology$$c2020$$dQ1
000117191 593__ $$aMolecular Biology$$c2020$$dQ1
000117191 593__ $$aMedicine (miscellaneous)$$c2020$$dQ1
000117191 593__ $$aGenetics$$c2020$$dQ1
000117191 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000117191 700__ $$aRivero, Maribel
000117191 700__ $$0(orcid)0000-0001-5823-7965$$aPolo, Victor$$uUniversidad de Zaragoza
000117191 700__ $$0(orcid)0000-0001-5702-4538$$aVelázquez-Campoy, Adrián$$uUniversidad de Zaragoza
000117191 700__ $$0(orcid)0000-0001-8743-0182$$aMedina, Milagros$$uUniversidad de Zaragoza
000117191 7102_ $$12012$$2755$$aUniversidad de Zaragoza$$bDpto. Química Física$$cÁrea Química Física
000117191 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000117191 773__ $$g34, 8 (2020), 10871-10886$$pFASEB j.$$tThe FASEB Journal$$x0892-6638
000117191 8564_ $$s1546014$$uhttps://zaguan.unizar.es/record/117191/files/texto_completo.pdf$$yVersión publicada
000117191 8564_ $$s2425556$$uhttps://zaguan.unizar.es/record/117191/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000117191 909CO $$ooai:zaguan.unizar.es:117191$$particulos$$pdriver
000117191 951__ $$a2022-06-17-14:31:34
000117191 980__ $$aARTICLE