57794 20200221144337.0 doi 10.1371/journal.pone.0161020 sideral 97103 ART-2016-97103 eng Rodríguez-Cardenas, Á. Streptococcus pneumoniae TIGR4 flavodoxin: Structural and biophysical characterization of a novel drug target 2016 Access copy available to the general public Unrestricted Streptococcus pneumoniae (Sp) strain TIGR4 is a virulent, encapsulated serotype that causes bacteremia, otitis media, meningitis and pneumonia. Increased bacterial resistance and limited efficacy of the available vaccine to some serotypes complicate the treatment of diseases associated to this microorganism. Flavodoxins are bacterial proteins involved in several important metabolic pathways. The Sp flavodoxin (Spfld) gene was recently reported to be essential for the establishment of meningitis in a rat model, which makes SpFld a potential drug target. To facilitate future pharmacological studies, we have cloned and expressed SpFld in E. coli and we have performed an extensive structural and biochemical characterization of both the apo form and its active complex with the FMN cofactor. SpFld is a short-chain flavodoxin containing 146 residues. Unlike the well-characterized long-chain apoflavodoxins, the Sp apoprotein displays a simple two-state thermal unfolding equilibrium and binds FMN with moderate affinity. The X-ray structures of the apo and holo forms of SpFld differ at the FMN binding site, where substantial rearrangement of residues at the 91-100 loop occurs to permit cofactor binding. This work will set up the basis for future studies aiming at discovering new potential drugs to treat S. pneumoniae diseases through the inhibition of SpFld. info:eu-repo/grantAgreement/ES/MINECO/BIO2014-57314-REDT info:eu-repo/grantAgreement/ES/MINECO/BFU2013-47064-P info:eu-repo/grantAgreement/ES/MICINN/CTQ2013-44367-C2-2-P info:eu-repo/grantAgreement/ES/MICINN/BFU2010-19504 info:eu-repo/grantAgreement/ES/MICINN/BFU2010-16297 info:eu-repo/grantAgreement/EC/FP7/283570/EU/Transnational access and enhancement of integrated Biological Structure determination at synchrotron X-ray radiation facilities/BIOSTRUCT-X info:eu-repo/grantAgreement/ES/DGA/B89 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 2.806 2016 MULTIDISCIPLINARY SCIENCES 15 / 63 = 0.238 2016 Q1 T1 1.236 2016 Agricultural and Biological Sciences (miscellaneous) 2016 Q1 Medicine (miscellaneous) 2016 Q1 Biochemistry, Genetics and Molecular Biology (miscellaneous) 2016 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Rojas, A.L. (orcid)0000-0003-4358-9110 Conde-Giménez, M. Universidad de Zaragoza (orcid)0000-0001-5702-4538 Velazquez-Campoy, A. Universidad de Zaragoza (orcid)0000-0002-3122-9401 Hurtado-Guerrero, R. Universidad de Zaragoza (orcid)0000-0002-2879-9200 Sancho, J. Universidad de Zaragoza 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 11, 9 (2016), 0161020 [25pp] PLoS One PloS one 1932-6203 1292762 http://zaguan.unizar.es/record/57794/files/texto_completo.pdf Versión publicada 68010 http://zaguan.unizar.es/record/57794/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:57794 articulos driver 2020-02-21-13:48:05 ARTICLE