70965 20201130083155.0 doi 10.1080/14756366.2018.1461857 sideral 106585 ART-2018-106585 eng (orcid)0000-0001-7202-4587 Sebastián, M. Universidad de Zaragoza The RFK catalytic cycle of the pathogen Streptococcus pneumoniae shows species-specific features in prokaryotic FMN synthesis 2018 Access copy available to the general public Unrestricted Emergence 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. info:eu-repo/grantAgreement/ES/MINECO/BIO2016-75183-P info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 4.027 2018 CHEMISTRY, MEDICINAL 9 / 61 = 0.148 2018 Q1 T1 BIOCHEMISTRY & MOLECULAR BIOLOGY 82 / 294 = 0.279 2018 Q2 T1 0.781 2018 Drug Discovery 2018 Q2 Pharmacology 2018 Q2 Medicine (miscellaneous) 2018 Q2 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion (orcid)0000-0001-5702-4538 Velázquez-Campoy, A. Universidad de Zaragoza (orcid)0000-0001-8743-0182 Medina, M. Universidad de Zaragoza 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 33, 1 (2018), 842-849 J. Enzym. Inhib. Med. Chem. Journal of Enzyme Inhibition and Medicinal Chemistry 1475-6366 1367836 http://zaguan.unizar.es/record/70965/files/texto_completo.pdf Versión publicada 141326 http://zaguan.unizar.es/record/70965/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:70965 articulos driver 2020-11-30-07:57:13 ARTICLE