{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:35:08Z","timestamp":1790876108631,"version":"4.1.0"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,8,8]],"date-time":"2017-08-08T00:00:00Z","timestamp":1502150400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,8,8]],"date-time":"2017-08-08T00:00:00Z","timestamp":1502150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Prokaryotic bifunctional FAD synthetases (FADSs) catalyze the biosynthesis of FMN and FAD, whereas in eukaryotes two enzymes are required for the same purpose. FMN and FAD are key cofactors to maintain the flavoproteome homeostasis in all type of organisms. Here we shed light to the properties of the hitherto unstudied bacterial FADS from the human pathogen <jats:italic>Streptococcus pneumoniae<\/jats:italic> (<jats:italic>Spn<\/jats:italic>FADS). As other members of the family, <jats:italic>Spn<\/jats:italic>FADS catalyzes the three typical activities of prokaryotic FADSs: riboflavin kinase (RFK), ATP:FMN:adenylyltransferase (FMNAT), and FAD pyrophosphorylase (FADpp). However, several <jats:italic>Spn<\/jats:italic>FADS biophysical properties differ from those of other family members. In particular; i) the RFK activity is not inhibited by the riboflavin (RF) substrate, ii) the FMNAT and FADSpp activities require flavin substrates in the reduced state, iii) binding of adenine nucleotide ligands is required for the binding of flavinic substrates\/products and iv) the monomer is the preferred state. Collectively, our results add interesting mechanistic differences among the few prokaryotic bifunctional FADSs already characterized, which might reflect the adaptation of the enzyme to relatively different environments. In a health point of view, differences among FADS family members provide us with a framework to design selective compounds targeting these enzymes for the treatment of diverse infectious diseases.<\/jats:p>","DOI":"10.1038\/s41598-017-07716-5","type":"journal-article","created":{"date-parts":[[2017,8,2]],"date-time":"2017-08-02T11:57:54Z","timestamp":1501675074000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["The FAD synthetase from the human pathogen Streptococcus pneumoniae: a bifunctional enzyme exhibiting activity-dependent redox requirements"],"prefix":"10.1038","volume":"7","author":[{"given":"Mar\u00eda","family":"Sebasti\u00e1n","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erandi","family":"Lira-Navarrete","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Serrano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Marcuello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adri\u00e1n","family":"Vel\u00e1zquez-Campoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7460-5916","authenticated-orcid":false,"given":"Anabel","family":"Lostao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram\u00f3n","family":"Hurtado-Guerrero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8743-0182","authenticated-orcid":false,"given":"Milagros","family":"Medina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9047-0046","authenticated-orcid":false,"given":"Marta","family":"Mart\u00ednez-J\u00falvez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,8,8]]},"reference":[{"key":"7716_CR1","doi-asserted-by":"crossref","unstructured":"Frago, S., Vel\u00e1zquez-Campoy, A. & Medina, M. The puzzle of ligand binding to Corynebacterium ammoniagenes FAD synthetase. J Biol Chem \n                           284, 6610\u20136619, doi:M808142200 (2009).","DOI":"10.1074\/jbc.M808142200"},{"key":"7716_CR2","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1128\/JB.180.4.950-955.1998","volume":"180","author":"M Mack","year":"1998","unstructured":"Mack, M., van Loon, A. P. & Hohmann, H. P. Regulation of riboflavin biosynthesis in Bacillus subtilis is affected by the activity of the flavokinase\/flavin adenine dinucleotide synthetase encoded by ribC. J Bacteriol \n                           180, 950\u2013955 (1998).","journal-title":"J Bacteriol"},{"key":"7716_CR3","doi-asserted-by":"crossref","first-page":"16169","DOI":"10.1016\/S0021-9258(18)66693-1","volume":"261","author":"DJ Manstein","year":"1986","unstructured":"Manstein, D. J. & Pai, E. F. Purification and characterization of FAD synthetase from Brevibacterium ammoniagenes. J Biol Chem \n                           261, 16169\u201316173 (1986).","journal-title":"J Biol Chem"},{"key":"7716_CR4","doi-asserted-by":"crossref","first-page":"9551","DOI":"10.1016\/S0021-9258(19)83550-0","volume":"254","author":"EB Kearney","year":"1979","unstructured":"Kearney, E. B., Goldenberg, J., Lipsick, J. & Perl, M. Flavokinase and FAD synthetase from Bacillus subtilis specific for reduced flavins. J Biol Chem \n                           254, 9551\u20139557 (1979).","journal-title":"J Biol Chem"},{"key":"7716_CR5","doi-asserted-by":"publisher","first-page":"14492","DOI":"10.3390\/ijms131114492","volume":"13","author":"A Serrano","year":"2012","unstructured":"Serrano, A., Frago, S., Vel\u00e1zquez-Campoy, A. & Medina, M. Role of key residues at the flavin mononucleotide (FMN):adenylyltransferase catalytic site of the bifunctional riboflavin kinase\/flavin adenine dinucleotide (FAD) Synthetase from Corynebacterium ammoniagenes. Int J Mol Sci \n                           13, 14492\u201314517, doi:10.3390\/ijms131114492 (2012).","journal-title":"Int J Mol Sci"},{"key":"7716_CR6","doi-asserted-by":"publisher","first-page":"4346","DOI":"10.1046\/j.1432-1327.2000.01464.x","volume":"267","author":"C Brizio","year":"2000","unstructured":"Brizio, C., Otto, A., Brandsch, R., Passarella, S. & Barile, M. A protein factor of rat liver mitochondrial matrix involved in flavinylation of dimethylglycine dehydrogenase. Eur J Biochem \n                           267, 4346\u20134354 (2000).","journal-title":"Eur J Biochem"},{"key":"7716_CR7","doi-asserted-by":"publisher","first-page":"4888","DOI":"10.1046\/j.1432-1327.2000.01552.x","volume":"267","author":"M Barile","year":"2000","unstructured":"Barile, M., Brizio, C., Valenti, D., De Virgilio, C. & Passarella, S. The riboflavin\/FAD cycle in rat liver mitochondria. Eur J Biochem \n                           267, 4888\u20134900 (2000).","journal-title":"Eur J Biochem"},{"key":"7716_CR8","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1186\/1471-2148-10-311","volume":"10","author":"I Yruela","year":"2010","unstructured":"Yruela, I., Arilla-Luna, S., Medina, M. & Contreras-Moreira, B. Evolutionary divergence of chloroplasts FAD synthetase proteins. BMC Evol Biol \n                           10, 311 (2010).","journal-title":"BMC Evol Biol"},{"key":"7716_CR9","doi-asserted-by":"publisher","first-page":"8748","DOI":"10.1021\/bi100817q","volume":"49","author":"Z Mashhadi","year":"2010","unstructured":"Mashhadi, Z., Xu, H., Grochowski, L. L. & White, R. H. Archaeal RibL: a new FAD synthetase that is air sensitive. Biochemistry \n                           49, 8748\u20138755, doi:10.1021\/bi100817q (2010).","journal-title":"Biochemistry"},{"key":"7716_CR10","doi-asserted-by":"crossref","unstructured":"Herguedas, B., Martinez-Julvez, M., Frago, S., Medina, M. & Hermoso, J. A. Oligomeric state in the crystal structure of modular FAD synthetase provides insights into its sequential catalysis in prokaryotes. J Mol Biol \n                           400, 218\u2013230, doi:S0022-2836(10)00497-3 (2010).","DOI":"10.1016\/j.jmb.2010.05.018"},{"key":"7716_CR11","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1002\/prot.20207","volume":"58","author":"W Wang","year":"2005","unstructured":"Wang, W., Kim, R., Yokota, H. & Kim, S. H. Crystal structure of flavin binding to FAD synthetase of Thermotoga maritima. Proteins \n                           58, 246\u2013248, doi:10.1002\/prot.20207 (2005).","journal-title":"Proteins"},{"key":"7716_CR12","doi-asserted-by":"crossref","unstructured":"Karthikeyan, S. et al. Crystal structure of human riboflavin kinase reveals a beta barrel fold and a novel active site arch. Structure \n                           11, 265\u2013273, doi:S0969212603000248 (2003).","DOI":"10.1016\/S0969-2126(03)00024-8"},{"key":"7716_CR13","doi-asserted-by":"crossref","unstructured":"Frago, S., Mart\u00ednez-J\u00falvez, M., Serrano, A. & Medina, M. Structural analysis of FAD synthetase from Corynebacterium ammoniagenes. BMC Microbiol \n                           8, 160, doi:1471-2180-8-160 (2008).","DOI":"10.1186\/1471-2180-8-160"},{"key":"7716_CR14","doi-asserted-by":"crossref","unstructured":"Huerta, C., Borek, D., Machius, M., Grishin, N. V. & Zhang, H. Structure and mechanism of a eukaryotic FMN adenylyltransferase. J Mol Biol \n                           389, 388\u2013400, doi:S0022-2836(09)00452-5 (2009).","DOI":"10.1016\/j.jmb.2009.04.022"},{"key":"7716_CR15","doi-asserted-by":"crossref","unstructured":"Krupa, A., Sandhya, K., Srinivasan, N. & Jonnalagadda, S. A conserved domain in prokaryotic bifunctional FAD synthetases can potentially catalyze nucleotide transfer. Trends Biochem Sci \n                           28, 9\u201312, doi:S0968000402000099 (2003).","DOI":"10.1016\/S0968-0004(02)00009-9"},{"key":"7716_CR16","doi-asserted-by":"publisher","first-page":"2625","DOI":"10.1111\/j.1742-4658.2011.08202.x","volume":"278","author":"P Macheroux","year":"2011","unstructured":"Macheroux, P., Kappes, B. & Ealick, S. E. Flavogenomics-a genomic and structural view of flavin-dependent proteins. Febs J \n                           278, 2625\u20132634, doi:10.1111\/j.1742-4658.2011.08202.x (2011).","journal-title":"Febs J"},{"key":"7716_CR17","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1042\/bst0280283","volume":"28","author":"V Massey","year":"2000","unstructured":"Massey, V. The chemical and biological versatility of riboflavin. Biochem Soc Trans \n                           28, 283\u2013296 (2000).","journal-title":"Biochem Soc Trans"},{"key":"7716_CR18","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1139\/o91-073","volume":"69","author":"HG Parsons","year":"1991","unstructured":"Parsons, H. G. & Dias, V. C. Intramitochondrial fatty acid metabolism: riboflavin deficiency and energy production. Biochem Cell Biol \n                           69, 490\u2013497 (1991).","journal-title":"Biochem Cell Biol"},{"key":"7716_CR19","doi-asserted-by":"publisher","first-page":"3929","DOI":"10.1021\/bi0360408","volume":"43","author":"S Daff","year":"2004","unstructured":"Daff, S. An appraisal of multiple NADPH binding-site models proposed for cytochrome P450 reductase, NO synthase, and related diflavin reductase systems. Biochemistry \n                           43, 3929\u20133932, doi:10.1021\/bi0360408 (2004).","journal-title":"Biochemistry"},{"key":"7716_CR20","doi-asserted-by":"publisher","first-page":"8411","DOI":"10.1073\/pnas.94.16.8411","volume":"94","author":"M Wang","year":"1997","unstructured":"Wang, M. et al. Three-dimensional structure of NADPH-cytochrome P450 reductase: prototype for FMN- and FAD-containing enzymes. Proc Natl Acad Sci USA \n                           94, 8411\u20138416 (1997).","journal-title":"Proc Natl Acad Sci USA"},{"key":"7716_CR21","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1038\/17135","volume":"397","author":"SA Susin","year":"1999","unstructured":"Susin, S. A. et al. Molecular characterization of mitochondrial apoptosis-inducing factor. Nature \n                           397, 441\u2013446 (1999).","journal-title":"Nature"},{"key":"7716_CR22","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1146\/annurev.nu.08.070188.001431","volume":"8","author":"HB White","year":"1988","unstructured":"White, H. B. & Merrill, A. H. Riboflavin-binding proteins. Annu Rev Nutr \n                           8, 279\u2013299, doi:10.1146\/annurev.nu.08.070188.001431 (1988).","journal-title":"Annu Rev Nutr"},{"key":"7716_CR23","doi-asserted-by":"publisher","first-page":"41360","DOI":"10.1074\/jbc.M509549200","volume":"280","author":"F Forneris","year":"2005","unstructured":"Forneris, F., Binda, C., Vanoni, M. A., Battaglioli, E. & Mattevi, A. Human histone demethylase LSD1 reads the histone code. J Biol Chem \n                           280, 41360\u201341365, doi:10.1074\/jbc.M509549200 (2005).","journal-title":"J Biol Chem"},{"key":"7716_CR24","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1126\/science.1072113","volume":"297","author":"H Myllykallio","year":"2002","unstructured":"Myllykallio, H. et al. An alternative flavin-dependent mechanism for thymidylate synthesis. Science \n                           297, 105\u2013107, doi:10.1126\/science.1072113 (2002).","journal-title":"Science"},{"key":"7716_CR25","doi-asserted-by":"publisher","first-page":"8180","DOI":"10.1073\/pnas.0901330106","volume":"106","author":"H Nishimasu","year":"2009","unstructured":"Nishimasu, H. et al. Atomic structure of a folate\/FAD-dependent tRNA T54 methyltransferase. Proc Natl Acad Sci USA \n                           106, 8180\u20138185, doi:10.1073\/pnas.0901330106 (2009).","journal-title":"Proc Natl Acad Sci USA"},{"key":"7716_CR26","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/S0092-8674(04)00418-0","volume":"117","author":"E Gross","year":"2004","unstructured":"Gross, E., Kastner, D. B., Kaiser, C. A. & Fass, D. Structure of Ero1p, source of disulfide bonds for oxidative protein folding in the cell. Cell \n                           117, 601\u2013610 (2004).","journal-title":"Cell"},{"key":"7716_CR27","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.pbi.2008.09.002","volume":"12","author":"E Demarsy","year":"2009","unstructured":"Demarsy, E. & Fankhauser, C. Higher plants use LOV to perceive blue light. Curr Opin Plant Biol \n                           12, 69\u201374, doi:10.1016\/j.pbi.2008.09.002 (2009).","journal-title":"Curr Opin Plant Biol"},{"key":"7716_CR28","doi-asserted-by":"publisher","first-page":"e38226","DOI":"10.1371\/journal.pone.0038226","volume":"7","author":"I Kraiselburd","year":"2012","unstructured":"Kraiselburd, I. et al. A LOV protein modulates the physiological attributes of Xanthomonas axonopodis pv. citri relevant for host plant colonization. PLoS One \n                           7, e38226, doi:10.1371\/journal.pone.0038226 (2012).","journal-title":"PLoS One"},{"key":"7716_CR29","doi-asserted-by":"publisher","first-page":"1858","DOI":"10.1093\/pcp\/pcu103","volume":"55","author":"S Masuda","year":"2014","unstructured":"Masuda, S. Light Detection and Signal Transduction in the BLUF Photoreceptors. Plant Cell Physiol \n                           55, 1858, doi:10.1093\/pcp\/pcu103 (2014).","journal-title":"Plant Cell Physiol"},{"key":"7716_CR30","doi-asserted-by":"publisher","first-page":"4749","DOI":"10.1021\/acs.jpclett.5b02245","volume":"6","author":"J Mehlhorn","year":"2015","unstructured":"Mehlhorn, J. et al. Light-Induced Rearrangement of the \u03b25 Strand in the BLUF Photoreceptor SyPixD (Slr1694). J Phys Chem Lett \n                           6, 4749\u20134753, doi:10.1021\/acs.jpclett.5b02245 (2015).","journal-title":"J Phys Chem Lett"},{"key":"7716_CR31","doi-asserted-by":"publisher","first-page":"2146","DOI":"10.1002\/1873-3468.12227","volume":"590","author":"M Tanwar","year":"2016","unstructured":"Tanwar, M., Nahar, S., Gulati, S., Veetil, S. K. & Kateriya, S. Molecular determinant modulates thermal recovery kinetics and structural integrity of the bacterial BLUF photoreceptor. FEBS Lett \n                           590, 2146\u20132157, doi:10.1002\/1873-3468.12227 (2016).","journal-title":"FEBS Lett"},{"key":"7716_CR32","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1002\/prot.10353","volume":"52","author":"W Wang","year":"2003","unstructured":"Wang, W., Kim, R., Jancarik, J., Yokota, H. & Kim, S. H. Crystal structure of a flavin-binding protein from Thermotoga maritima. Proteins \n                           52, 633\u2013635, doi:10.1002\/prot.10353 (2003).","journal-title":"Proteins"},{"key":"7716_CR33","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/s12013-012-9403-9","volume":"65","author":"A Serrano","year":"2013","unstructured":"Serrano, A. et al. Key residues at the riboflavin kinase catalytic site of the bifunctional riboflavin kinase\/FMN adenylyltransferase from Corynebacterium ammoniagenes. Cell Biochem Biophys \n                           65, 57\u201368, doi:10.1007\/s12013-012-9403-9 (2013).","journal-title":"Cell Biochem Biophys"},{"key":"7716_CR34","doi-asserted-by":"crossref","unstructured":"Grill, S., Busenbender, S., Pfeiffer, M., Kohler, U. & Mack, M. The bifunctional flavokinase\/flavin adenine dinucleotide synthetase from Streptomyces davawensis produces inactive flavin cofactors and is not involved in resistance to the antibiotic roseoflavin. J Bacteriol \n                           190, 1546\u20131553, doi:JB.01586-07 (2008).","DOI":"10.1128\/JB.01586-07"},{"key":"7716_CR35","doi-asserted-by":"publisher","first-page":"3233","DOI":"10.1128\/JB.00388-16","volume":"198","author":"A Matern","year":"2016","unstructured":"Matern, A., Pedrolli, D., Gro\u00dfhennig, S., Johansson, J. & Mack, M. Uptake and Metabolism of Antibiotics Roseoflavin and 8-Demethyl-8-Aminoriboflavin in Riboflavin-Auxotrophic Listeria monocytogenes. J Bacteriol \n                           198, 3233\u20133243, doi:10.1128\/JB.00388-16 (2016).","journal-title":"J Bacteriol"},{"key":"7716_CR36","doi-asserted-by":"publisher","first-page":"2526","DOI":"10.1107\/S1399004715019641","volume":"71","author":"B Herguedas","year":"2015","unstructured":"Herguedas, B. et al. Structural insights into the synthesis of FMN in prokaryotic organisms. Acta Crystallogr D Biol Crystallogr \n                           71, 2526\u20132542, doi:10.1107\/S1399004715019641 (2015).","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"7716_CR37","doi-asserted-by":"publisher","first-page":"2637","DOI":"10.2174\/1381612811319140013","volume":"19","author":"A Serrano","year":"2013","unstructured":"Serrano, A., Ferreira, P., Mart\u00ednez-J\u00falvez, M. & Medina, M. The prokaryotic FAD synthetase family: a potential drug target. Curr Pharm Des \n                           19, 2637\u20132648 (2013).","journal-title":"Curr Pharm Des"},{"key":"7716_CR38","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1016\/S0140-6736(09)61204-6","volume":"374","author":"KL O\u2019Brien","year":"2009","unstructured":"O\u2019Brien, K. L. et al. Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates. Lancet \n                           374, 893\u2013902, doi:10.1016\/S0140-6736(09)61204-6 (2009).","journal-title":"Lancet"},{"key":"7716_CR39","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1111\/j.1469-0691.2010.03183.x","volume":"16","author":"AM Mitchell","year":"2010","unstructured":"Mitchell, A. M. & Mitchell, T. J. Streptococcus pneumoniae: virulence factors and variation. Clin Microbiol Infect \n                           16, 411\u2013418, doi:10.1111\/j.1469-0691.2010.03183.x (2010).","journal-title":"Clin Microbiol Infect"},{"key":"7716_CR40","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1093\/clinids\/14.4.801","volume":"14","author":"DM Musher","year":"1992","unstructured":"Musher, D. M. Infections caused by Streptococcus pneumoniae: clinical spectrum, pathogenesis, immunity, and treatment. Clin Infect Dis \n                           14, 801\u2013807 (1992).","journal-title":"Clin Infect Dis"},{"key":"7716_CR41","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/S0003-2697(03)00285-9","volume":"319","author":"V Raussens","year":"2003","unstructured":"Raussens, V., Ruysschaert, J. M. & Goormaghtigh, E. Protein concentration is not an absolute prerequisite for the determination of secondary structure from circular dichroism spectra: a new scaling method. Anal Biochem \n                           319, 114\u2013121 (2003).","journal-title":"Anal Biochem"},{"key":"7716_CR42","doi-asserted-by":"crossref","unstructured":"Pedrolli, D. B. et al. The antibiotics roseoflavin and 8-demethyl-8-amino-riboflavin from Streptomyces davawensis are metabolized by human flavokinase and human FAD synthetase. Biochem Pharmacol \n                           82, 1853\u20131859, doi:S0006-2952(11)00680-0 (2011).","DOI":"10.1016\/j.bcp.2011.08.029"},{"key":"7716_CR43","doi-asserted-by":"publisher","first-page":"4037","DOI":"10.1128\/JB.00646-13","volume":"195","author":"S Langer","year":"2013","unstructured":"Langer, S., Hashimoto, M., Hobl, B., Mathes, T. & Mack, M. Flavoproteins are potential targets for the antibiotic roseoflavin in Escherichia coli. J Bacteriol \n                           195, 4037\u20134045, doi:10.1128\/JB.00646-13 (2013).","journal-title":"J Bacteriol"},{"key":"7716_CR44","doi-asserted-by":"publisher","first-page":"9716","DOI":"10.1021\/bi972817j","volume":"37","author":"I Efimov","year":"1998","unstructured":"Efimov, I., Kuusk, V., Zhang, X. & McIntire, W. S. Proposed steady-state kinetic mechanism for Corynebacterium ammoniagenes FAD synthetase produced by Escherichia coli. Biochemistry \n                           37, 9716\u20139723, doi:10.1021\/bi972817j (1998).","journal-title":"Biochemistry"},{"key":"7716_CR45","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1096\/fasebj.9.7.7737454","volume":"9","author":"V Massey","year":"1995","unstructured":"Massey, V. Introduction: flavoprotein structure and mechanism. FASEB J \n                           9, 473\u2013475 (1995).","journal-title":"FASEB J"},{"key":"7716_CR46","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1039\/cs9821100015","volume":"11","author":"PF Heelis","year":"1982","unstructured":"Heelis, P. F. The photophysical and photochemical properties of flavins (isoalloxazines). Chem Soc Rev \n                           11, 15\u201339 (1982).","journal-title":"Chem Soc Rev"},{"key":"7716_CR47","doi-asserted-by":"crossref","unstructured":"Marcuello, C., Arilla-Luna, S., Medina, M. & Lostao, A. Detection of a quaternary organization into dimer of trimers of Corynebacterium ammoniagenes FAD synthetase at the single-molecule level and at the in cell level. Biochim Biophys Acta \n                           1834, 665\u2013676, doi:S1570-9639(12)00293-2 (2013).","DOI":"10.1016\/j.bbapap.2012.12.013"},{"key":"7716_CR48","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1016\/j.bbapap.2015.03.005","volume":"1854","author":"A Serrano","year":"2015","unstructured":"Serrano, A. et al. Quaternary organization in a bifunctional prokaryotic FAD synthetase: Involvement of an arginine at its adenylyltransferase module on the riboflavin kinase activity. Biochim Biophys Acta \n                           1854, 897\u2013906, doi:10.1016\/j.bbapap.2015.03.005 (2015).","journal-title":"Biochim Biophys Acta"},{"key":"7716_CR49","doi-asserted-by":"publisher","first-page":"30","DOI":"10.3389\/fchem.2015.00030","volume":"3","author":"TA Giancaspero","year":"2015","unstructured":"Giancaspero, T. A. et al. Remaining challenges in cellular flavin cofactor homeostasis and flavoprotein biogenesis. Front Chem \n                           3, 30, doi:10.3389\/fchem.2015.00030 (2015).","journal-title":"Front Chem"},{"key":"7716_CR50","doi-asserted-by":"publisher","unstructured":"Horcas, I. et al. WSXM: A software for scanning probe microscopy and a tool for nanotechnology. Review of Scientific Instruments \n                           78, doi:Artn 013705 doi:10.1063\/1.2432410 (2007).","DOI":"10.1063\/1.2432410"},{"key":"7716_CR51","doi-asserted-by":"crossref","unstructured":"Lostao, A., Peleato, M. L., Gomez-Moreno, C. & Fillat, M. F. Oligomerization properties of FurA from the cyanobacterium Anabaena sp. PCC 7120: direct visualization by in situ atomic force microscopy under different redox conditions. Biochim Biophys Acta 1804, 1723\u20131729, doi:S1570-9639(10)00100-7 (2010).","DOI":"10.1016\/j.bbapap.2010.04.002"},{"key":"7716_CR52","unstructured":"Delano, W. L. They PyMOL molecular graphics system. DeLano Scientific, San Carlos, CA, USA, http:\/\/www.pymol.org (2002)."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-07716-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-07716-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-07716-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T08:14:48Z","timestamp":1671783288000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-07716-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,8]]},"references-count":52,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["7716"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-07716-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,8]]},"assertion":[{"value":"2 May 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 June 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 August 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"7609"}}