000057794 001__ 57794
000057794 005__ 20200221144337.0
000057794 0247_ $$2doi$$a10.1371/journal.pone.0161020
000057794 0248_ $$2sideral$$a97103
000057794 037__ $$aART-2016-97103
000057794 041__ $$aeng
000057794 100__ $$aRodríguez-Cardenas, Á.
000057794 245__ $$aStreptococcus pneumoniae TIGR4 flavodoxin: Structural and biophysical characterization of a novel drug target
000057794 260__ $$c2016
000057794 5060_ $$aAccess copy available to the general public$$fUnrestricted
000057794 5203_ $$aStreptococcus 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.
000057794 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/BIO2014-57314-REDT$$9info:eu-repo/grantAgreement/ES/MINECO/BFU2013-47064-P$$9info:eu-repo/grantAgreement/ES/MICINN/CTQ2013-44367-C2-2-P$$9info:eu-repo/grantAgreement/ES/MICINN/BFU2010-19504$$9info:eu-repo/grantAgreement/ES/MICINN/BFU2010-16297$$9info:eu-repo/grantAgreement/EC/FP7/283570/EU/Transnational access and enhancement of integrated Biological Structure determination at synchrotron X-ray radiation facilities/BIOSTRUCT-X$$9info:eu-repo/grantAgreement/ES/DGA/B89
000057794 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000057794 590__ $$a2.806$$b2016
000057794 591__ $$aMULTIDISCIPLINARY SCIENCES$$b15 / 63 = 0.238$$c2016$$dQ1$$eT1
000057794 592__ $$a1.236$$b2016
000057794 593__ $$aAgricultural and Biological Sciences (miscellaneous)$$c2016$$dQ1
000057794 593__ $$aMedicine (miscellaneous)$$c2016$$dQ1
000057794 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2016$$dQ1
000057794 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000057794 700__ $$aRojas, A.L.
000057794 700__ $$0(orcid)0000-0003-4358-9110$$aConde-Giménez, M.$$uUniversidad de Zaragoza
000057794 700__ $$0(orcid)0000-0001-5702-4538$$aVelazquez-Campoy, A.$$uUniversidad de Zaragoza
000057794 700__ $$0(orcid)0000-0002-3122-9401$$aHurtado-Guerrero, R.$$uUniversidad de Zaragoza
000057794 700__ $$0(orcid)0000-0002-2879-9200$$aSancho, J.$$uUniversidad de Zaragoza
000057794 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000057794 773__ $$g11, 9 (2016), 0161020 [25pp]$$pPLoS One$$tPloS one$$x1932-6203
000057794 8564_ $$s1292762$$uhttps://zaguan.unizar.es/record/57794/files/texto_completo.pdf$$yVersión publicada
000057794 8564_ $$s68010$$uhttps://zaguan.unizar.es/record/57794/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000057794 909CO $$ooai:zaguan.unizar.es:57794$$particulos$$pdriver
000057794 951__ $$a2020-02-21-13:48:05
000057794 980__ $$aARTICLE