000096805 001__ 96805
000096805 005__ 20201130083156.0
000096805 0247_ $$2doi$$a10.1016/j.jmb.2019.05.029
000096805 0248_ $$2sideral$$a113145
000096805 037__ $$aART-2019-113145
000096805 041__ $$aeng
000096805 100__ $$0(orcid)0000-0001-7202-4587$$aSebastian, M.
000096805 245__ $$aThe Biosynthesis of Flavin Cofactors in Listeria monocytogenes
000096805 260__ $$c2019
000096805 5060_ $$aAccess copy available to the general public$$fUnrestricted
000096805 5203_ $$aListeria monocytogenes is riboflavin auxotrophic, but it has two genes envisaged to transform riboflavin into FMN and FAD after its uptaked by specialized transporters. One encodes a bifunctional type I FAD synthase (FADS, herein LmFADS-1), while the other produces a protein similar to type I at the FMN:ATP adenylyltransferase (FMNAT) site but with a shorter C-terminal that lacks any riboflavin kinase (RFK) motif. This second protein is rare among bacteria and has been named FADS type II (LmFADS-2). Here we present a biochemical and biophysical study of LmFADS-1 and LmFADS-2 by integrating kinetic and thermodynamic data together with sequence and structural prediction methods to evaluate their occurrence in Listeria, as well as their function and molecular properties. Despite LmFADS-1 similarities to other type I FADSs, (i) its RFK activity has not riboflavin substrate inhibition and occurs under reducing and oxidizing conditions, (ii) its FMNAT activity requires strong reducing environment, and (iii) binding of reaction products, but not substrates, favors binding of the second ligand. LmFADS-2 produces FAD under oxidizing and reducing environments, but its C-terminus module function remains unknown. Listeria species conserve both FADSs, being sequence identity high within L. monocytogenes strains. Our data exemplify alternative strategies for FMN and FAD biosynthesis and homeostasis, envisaging that in Listeria two FADSs might be required to fulfill the supply of flavin cofactors under niches that can go from saprophytism to virulence. As FADSs are attractive antimicrobial targets, understanding of FADSs traits in different species is essential to help in the discovery of specific antimicrobials.
000096805 536__ $$9info:eu-repo/grantAgreement/ES/DGA-FEDER/E35-17R$$9info:eu-repo/grantAgreement/ES/MINECO-AEI-FEDER/BIO2016-75183-P
000096805 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000096805 590__ $$a4.76$$b2019
000096805 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b68 / 297 = 0.229$$c2019$$dQ1$$eT1
000096805 592__ $$a3.268$$b2019
000096805 593__ $$aBiophysics$$c2019$$dQ1
000096805 593__ $$aStructural Biology$$c2019$$dQ1
000096805 593__ $$aMolecular Biology$$c2019$$dQ1
000096805 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000096805 700__ $$aArilla-Luna, S.
000096805 700__ $$aBellalou, J.
000096805 700__ $$0(orcid)0000-0003-3608-4720$$aYruela, I.$$uUniversidad de Zaragoza
000096805 700__ $$0(orcid)0000-0001-8743-0182$$aMedina, M.$$uUniversidad de Zaragoza
000096805 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000096805 773__ $$g431, 15 (2019), 2762-2776$$pJ. Mol. Biol.$$tJOURNAL OF MOLECULAR BIOLOGY$$x0022-2836
000096805 8564_ $$s759343$$uhttps://zaguan.unizar.es/record/96805/files/texto_completo.pdf$$yVersión publicada
000096805 8564_ $$s18790$$uhttps://zaguan.unizar.es/record/96805/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000096805 909CO $$ooai:zaguan.unizar.es:96805$$particulos$$pdriver
000096805 951__ $$a2020-11-30-07:57:56
000096805 980__ $$aARTICLE