000070965 001__ 70965
000070965 005__ 20201130083155.0
000070965 0247_ $$2doi$$a10.1080/14756366.2018.1461857
000070965 0248_ $$2sideral$$a106585
000070965 037__ $$aART-2018-106585
000070965 041__ $$aeng
000070965 100__ $$0(orcid)0000-0001-7202-4587$$aSebastián, M.$$uUniversidad de Zaragoza
000070965 245__ $$aThe RFK catalytic cycle of the pathogen Streptococcus pneumoniae shows species-specific features in prokaryotic FMN synthesis
000070965 260__ $$c2018
000070965 5060_ $$aAccess copy available to the general public$$fUnrestricted
000070965 5203_ $$aEmergence of multidrug-resistant bacteria forces us to explore new therapeutic strategies, and proteins involved in key metabolic pathways are promising anti-bacterial targets. Bifunctional flavin-adenine dinucleotide (FAD) synthetases (FADS) are prokaryotic enzymes that synthesise the flavin mononucleotide (FMN) and FAD cofactors. The FADS from the human pathogen Streptococcus pneumoniae (SpnFADS)–causative agent of pneumonia in humans - shows relevant catalytic dissimilarities compared to other FADSs. Here, by integrating thermodynamic and kinetic data, we present a global description of the riboflavin kinase activity of SpnFADS, as well as of the inhibition mechanisms regulating this activity. Our data shed light on biophysical determinants that modulate species-specific conformational changes leading to catalytically competent conformations, as well as binding rates and affinities of substrates versus products. This knowledge paves the way for the development of tools - that taking advantage of the regulatory dissimilarities during FMN biosynthesis in different species - might be used in the discovery of specific anti-pneumococcal drugs.
000070965 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/BIO2016-75183-P
000070965 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000070965 590__ $$a4.027$$b2018
000070965 591__ $$aCHEMISTRY, MEDICINAL$$b9 / 61 = 0.148$$c2018$$dQ1$$eT1
000070965 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b82 / 294 = 0.279$$c2018$$dQ2$$eT1
000070965 592__ $$a0.781$$b2018
000070965 593__ $$aDrug Discovery$$c2018$$dQ2
000070965 593__ $$aPharmacology$$c2018$$dQ2
000070965 593__ $$aMedicine (miscellaneous)$$c2018$$dQ2
000070965 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000070965 700__ $$0(orcid)0000-0001-5702-4538$$aVelázquez-Campoy, A.$$uUniversidad de Zaragoza
000070965 700__ $$0(orcid)0000-0001-8743-0182$$aMedina, M.$$uUniversidad de Zaragoza
000070965 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000070965 773__ $$g33, 1 (2018), 842-849$$pJ. Enzym. Inhib. Med. Chem.$$tJournal of Enzyme Inhibition and Medicinal Chemistry$$x1475-6366
000070965 8564_ $$s1367836$$uhttps://zaguan.unizar.es/record/70965/files/texto_completo.pdf$$yVersión publicada
000070965 8564_ $$s141326$$uhttps://zaguan.unizar.es/record/70965/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000070965 909CO $$ooai:zaguan.unizar.es:70965$$particulos$$pdriver
000070965 951__ $$a2020-11-30-07:57:13
000070965 980__ $$aARTICLE