000089745 001__ 89745
000089745 005__ 20210902121805.0
000089745 0247_ $$2doi$$a10.3390/ijms21103738
000089745 0248_ $$2sideral$$a118161
000089745 037__ $$aART-2020-118161
000089745 041__ $$aeng
000089745 100__ $$aSerrano, A.$$uUniversidad de Zaragoza
000089745 245__ $$aInsights into the fmnat active site of fad synthase: Aromaticity is essential for flavin binding and catalysis
000089745 260__ $$c2020
000089745 5060_ $$aAccess copy available to the general public$$fUnrestricted
000089745 5203_ $$aThe last step in the biosynthesis of flavin adenine dinucleotide (FAD) is considered a target for the design of antimicrobial drugs because it is carried out by two non-homologous proteins in eukaryotic and prokaryotic organisms. Monofunctional FMN: adenylyltransferases (FMNAT) in Eukarya and FMNAT modules of bifunctional FAD synthases (FADS) in Prokarya belong to different structural families with dissimilar chemistry and binding modes for the substrates. In this study, we analyzed the relevance of the hydrophobic environment of the flavin isoalloxazine in the FMNAT active site of Corynebacterium ammoniagenes FADS (CaFADS) through the mutational analysis of its F62, Y106, and F128 residues. They form the isoalloxazine binding cavity and are highly conserved in the prokaryotic FADS family. The spectroscopic, steady-state kinetics and thermodynamic data presented indicate that distortion of aromaticity at the FMNAT isoalloxazine binding cavity prevents FMN and FAD from correct accommodation in their binding cavity and, as a consequence, decreases the efficiency of the FMNAT activity. Therefore, the side-chains of F62, Y106 and F128 are relevant in the formation of the catalytic competent complex during FMNAT catalysis in CaFADS. The introduced mutations also modulate the activity occurring at the riboflavin kinase (RFK) module of CaFADS, further evidencing the formation of quaternary assemblies during catalysis.
000089745 536__ $$9info:eu-repo/grantAgreement/ES/DGA-FEDER/E35-20R$$9info:eu-repo/grantAgreement/ES/MINECO-AEI-FEDER/BIO2016-75183-P
000089745 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000089745 590__ $$a5.923$$b2020
000089745 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b67 / 297 = 0.226$$c2020$$dQ1$$eT1
000089745 591__ $$aCHEMISTRY, MULTIDISCIPLINARY$$b49 / 178 = 0.275$$c2020$$dQ2$$eT1
000089745 592__ $$a1.455$$b2020
000089745 593__ $$aCatalysis$$c2020$$dQ1
000089745 593__ $$aComputer Science Applications$$c2020$$dQ1
000089745 593__ $$aInorganic Chemistry$$c2020$$dQ1
000089745 593__ $$aSpectroscopy$$c2020$$dQ1
000089745 593__ $$aMolecular Biology$$c2020$$dQ1
000089745 593__ $$aOrganic Chemistry$$c2020$$dQ1
000089745 593__ $$aPhysical and Theoretical Chemistry$$c2020$$dQ1
000089745 593__ $$aMedicine (miscellaneous)$$c2020$$dQ1
000089745 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000089745 700__ $$aArilla-Luna, S.
000089745 700__ $$0(orcid)0000-0001-8743-0182$$aMedina, M.$$uUniversidad de Zaragoza
000089745 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000089745 773__ $$g21, 10 (2020), 3738 [16 pp]$$pInt. j. mol. sci.$$tInternational Journal of Molecular Sciences$$x1661-6596
000089745 8564_ $$s1011542$$uhttps://zaguan.unizar.es/record/89745/files/texto_completo.pdf$$yVersión publicada
000089745 8564_ $$s514768$$uhttps://zaguan.unizar.es/record/89745/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000089745 909CO $$ooai:zaguan.unizar.es:89745$$particulos$$pdriver
000089745 951__ $$a2021-09-02-09:57:49
000089745 980__ $$aARTICLE