{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:59:45Z","timestamp":1787021985106,"version":"build-2736575974"},"reference-count":63,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2016,9,20]],"date-time":"2016-09-20T00:00:00Z","timestamp":1474329600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0161020","type":"journal-article","created":{"date-parts":[[2016,9,20]],"date-time":"2016-09-20T13:31:27Z","timestamp":1474378287000},"page":"e0161020","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Streptococcus pneumoniae TIGR4 Flavodoxin: Structural and Biophysical Characterization of a Novel Drug Target"],"prefix":"10.1371","volume":"11","author":[{"given":"\u00c1ngela","family":"Rodr\u00edguez-C\u00e1rdenas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana L.","family":"Rojas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Conde-Gim\u00e9nez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adri\u00e1n","family":"Vel\u00e1zquez-Campoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram\u00f3n","family":"Hurtado-Guerrero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Sancho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2016,9,20]]},"reference":[{"issue":"4","key":"ref1","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1128\/MMBR.59.4.591-603.1995","article-title":"Streptococcus pneumoniae: virulence factors, pathogenesis, and vaccines","volume":"59","author":"E AlonsoDeVelasco","year":"1995","journal-title":"Microbiological Reviews"},{"issue":"39","key":"ref2","doi-asserted-by":"crossref","first-page":"12390","DOI":"10.1021\/bi049131t","article-title":"Expression and characterization of the two flavodoxin proteins of Bacillus subtilis, YkuN and YkuP: biophysical properties and interactions with cytochrome P450 BioI","volume":"43","author":"RJ Lawson","year":"2004","journal-title":"Biochemistry"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1111\/j.1469-0691.2010.03183.x","article-title":"Streptococcus pneumoniae: virulence factors and variation","volume":"16","author":"AM Mitchell","year":"2010","journal-title":"Clinical Microbiology and Infection"},{"issue":"12","key":"ref4","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1056\/NEJMoa022521","article-title":"An Outbreak of Conjunctivitis Due to Atypical Streptococcus pneumoniae","volume":"348","author":"M Martin","year":"2003","journal-title":"New England Journal of Medicine"},{"issue":"32","key":"ref5","first-page":"4717","article-title":"Pneumococcal vaccines WHO position paper -2012- Recommendations","volume":"30","author":"P WHO","journal-title":"Vaccine"},{"issue":"1","key":"ref6","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.3390\/ijms14011152","article-title":"Structural and phylogenetic analysis of Rhodobacter capsulatus NifF: Uncovering general features of nitrogen-fixation (nif)-flavodoxins","volume":"14","author":"I P\u00e9rez-Dorado","year":"2013","journal-title":"International Journal of Molecular Sciences"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1111\/j.1469-0691.2010.03182.x","article-title":"Changes in antimicrobial resistance, serotypes and genotypes in Streptococcus pneumoniae over a 30-year period","volume":"16","author":"J Li\u00f1ares","year":"2010","journal-title":"Clinical Microbiology and Infection"},{"issue":"6","key":"ref8","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1038\/ng.2625","article-title":"Population genomics of post-vaccine changes inpneumococcal epidemiology","volume":"45","author":"NJ Croucher","year":"2013","journal-title":"Nature genetics"},{"issue":"1","key":"ref9","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1128\/IAI.00631-10","article-title":"Genome-wide identification of Streptococcus pneumoniae genes essential for bacterial replication during experimental meningitis","volume":"79","author":"TE Molzen","year":"2011","journal-title":"Infection and Immunity"},{"issue":"5529","key":"ref10","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1126\/science.1061217","article-title":"Complete Genome Sequence of a Virulent Isolate of Streptococcus pneumoniae","volume":"293","author":"H Tettelin","year":"2001","journal-title":"Science"},{"issue":"Database issue","key":"ref11","doi-asserted-by":"crossref","first-page":"D455","DOI":"10.1093\/nar\/gkn858","article-title":"DEG 5.0, a database of essential genes in both prokaryotes and eukaryotes","volume":"37","author":"R Zhang","year":"2009","journal-title":"Nucleic Acids Research"},{"issue":"19","key":"ref12","doi-asserted-by":"crossref","first-page":"5673","DOI":"10.1128\/JB.185.19.5673-5684.2003","article-title":"Experimental Determination and System Level Analysis of Essential Genes in Escherichia coli MG1655","volume":"185","author":"SY Gerdes","year":"2003","journal-title":"Journal of Bacteriology"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"2006.0008","DOI":"10.1038\/msb4100050","article-title":"Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection","volume":"2","author":"T Baba","year":"2006","journal-title":"Molecular Systems Biology"},{"issue":"12","key":"ref14","doi-asserted-by":"crossref","first-page":"2308","DOI":"10.1101\/gr.097097.109","article-title":"Simultaneous assay of every Salmonella Typhi gene using one million transposon mutants","volume":"19","author":"GC Langridge","year":"2009","journal-title":"Genome Research"},{"issue":"2","key":"ref15","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1073\/pnas.012602299","article-title":"A genome-scale analysis for identification of genes required for growth or survival of Haemophilus influenzae","volume":"99","author":"BJ Akerley","year":"2002","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"25","key":"ref16","doi-asserted-by":"crossref","first-page":"8736","DOI":"10.1073\/pnas.0803281105","article-title":"A defined transposon mutant library and its use in identifying motility genes in Vibrio cholerae","volume":"105","author":"DE Cameron","year":"2008","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"2","key":"ref17","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1110\/ps.28602","article-title":"Crystal structure of oxidized flavodoxin, an essential protein in Helicobacter pylori. Protein Science","volume":"11","author":"J Freigang","year":"2002","journal-title":"A Publication of the Protein Society"},{"issue":"7","key":"ref18","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1007\/s00018-005-5514-4","article-title":"Flavodoxins: sequence, folding, binding, function and beyond","volume":"63","author":"J Sancho","year":"2006","journal-title":"Cellular and Molecular Life Sciences CMLS"},{"issue":"2","key":"ref19","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1128\/JB.141.2.470-475.1980","article-title":"Roles of nifF and nifJ gene products in electron transport to nitrogenase in Klebsiella pneumoniae","volume":"141","author":"S Hill","year":"1980","journal-title":"Journal of Bacteriology"},{"issue":"2","key":"ref20","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1006\/bbrc.1993.2548","article-title":"Flavodoxin Is Required for the Activation of the Anaerobic Ribonucleotide Reductase","volume":"197","author":"V Bianchi","year":"1993","journal-title":"Biochemical and Biophysical Research Communications"},{"issue":"21","key":"ref21","doi-asserted-by":"crossref","first-page":"6745","DOI":"10.1016\/S0021-9258(19)42122-4","article-title":"Activation of methionine synthetase by a reduced triphosphopyridine nucleotide-dependent flavoprotein system","volume":"249","author":"K Fujii","year":"1974","journal-title":"Journal of Biological Chemistry"},{"issue":"1","key":"ref22","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1111\/j.1432-1033.1994.tb20009.x","article-title":"Flavodoxin is Required for Conversion of Dethiobiotin to Biotin in Escherichia coli","volume":"224","author":"O Ifuku","year":"1994","journal-title":"European Journal of Biochemistry"},{"issue":"51","key":"ref23","doi-asserted-by":"crossref","first-page":"14102","DOI":"10.1021\/bi00214a005","article-title":"Molecular properties of pyruvate formate-lyase activating enzyme","volume":"32","author":"KK Wong","year":"1993","journal-title":"Biochemistry"},{"issue":"2\u20133","key":"ref24","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.bpc.2004.12.045","article-title":"Towards a newtherapeutic target: Helicobacter pylori flavodoxin","volume":"115","author":"N Cremades","year":"2005","journal-title":"Biophysical Chemistry"},{"issue":"13","key":"ref25","doi-asserted-by":"crossref","first-page":"4764","DOI":"10.1128\/JB.00287-07","article-title":"Flavodoxin:quinone reductase (FqrB): a redox partner of pyruvate:ferredoxin oxidoreductase that reversibly couples pyruvate oxidation to NADPH production in Helicobacter pylori and Campylobacter jejuni","volume":"189","author":"M St. Maurice","year":"2007","journal-title":"Journal of Bacteriology"},{"issue":"3","key":"ref26","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1002\/prot.21410","article-title":"Common conformational changes in flavodoxins induced by FMN and anion binding: The structure of Helicobacter pylori apoflavodoxin","volume":"69","author":"M Mart\u00ednez-J\u00falvez","year":"2007","journal-title":"Proteins: Structure, Function, and Bioinformatics"},{"issue":"5","key":"ref27","doi-asserted-by":"crossref","first-page":"2883","DOI":"10.1074\/jbc.M705677200","article-title":"Conformational Stability of Helicobacter pylori Flavodoxin: Fit to Function at pH 5","volume":"283","author":"N Cremades","year":"2008","journal-title":"Journal of Biological Chemistry"},{"issue":"2","key":"ref28","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1021\/bi701365e","article-title":"The flavodoxin from Helicobacter pylori: structural determinants of thermostability and FMN cofactor binding","volume":"47","author":"N Cremades","year":"2008","journal-title":"Biochemistry"},{"issue":"4","key":"ref29","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1529\/biophysj.108.130153","article-title":"Molten Globule and Native State Ensemble of Helicobacter pylori Flavodoxin: Can Crowding, Osmolytes or Cofactors Stabilize the Native Conformation Relative to the Molten Globule?","volume":"95","author":"N Cremades","year":"2008","journal-title":"Biophysical Journal"},{"issue":"40","key":"ref30","doi-asserted-by":"crossref","first-page":"8703","DOI":"10.1021\/bi201025y","article-title":"Mechanism of FMN Binding to the Apoflavodoxin from Helicobacter pylori","volume":"50","author":"S Ayuso-Tejedor","year":"2011","journal-title":"Biochemistry"},{"issue":"11","key":"ref31","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1021\/cb900166q","article-title":"Discovery of specific flavodoxin inhibitors as potential therapeutic agents against Helicobacter pylori infection","volume":"4","author":"N Cremades","year":"2009","journal-title":"ACS Chemical Biology"},{"issue":"15","key":"ref32","doi-asserted-by":"crossref","first-page":"6248","DOI":"10.1021\/jm400786q","article-title":"Improved flavodoxin inhibitors with potential therapeutic effects against Helicobacter pylori infection","volume":"56","author":"JJ Galano","year":"2013","journal-title":"Journal of Medicinal Chemistry"},{"issue":"4","key":"ref33","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.jmb.2010.12.027","article-title":"Structural Analysis of an Equilibrium Folding Intermediate in the Apoflavodoxin Native Ensemble by Small-Angle X-ray Scattering","volume":"406","author":"S Ayuso-Tejedor","year":"2011","journal-title":"Journal of Molecular Biology"},{"key":"ref34","first-page":"318","article-title":"Structure of the trigonal form of recombinant oxidized flavodoxin from Anabaena 7120 at 1.40 A resolution","volume":"51","author":"BM Burkhart","year":"1995"},{"key":"ref35","first-page":"1413","article-title":"<italic>Structure of the oxidized long-chain flavodoxin from Anabaena 7120 at 2 A resolution<\/italic>, in <italic>Protein Science<\/italic>: <italic>A Publication of the Protein Society<\/italic>","author":"ST Rao","year":"1992"},{"issue":"9","key":"ref36","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1110\/ps.051582605","article-title":"A crystallographic study of Cys69Ala flavodoxin II from Azotobacter vinelandii: Structural determinants of redox potential","volume":"14","author":"S Alagaratnam","year":"2005","journal-title":"Protein Science: A Publication of the Protein Society"},{"key":"ref37","first-page":"319","article-title":"Calculation of protein extinction coefficients from amino acid sequence data","volume":"182","author":"SC Gill","year":"1989"},{"issue":"4","key":"ref38","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/S0021-9258(18)91858-2","article-title":"Purification and Characterization of Flavodoxin from Peptostreptococcus elsdenii","volume":"244","author":"SG Mayhew","year":"1969","journal-title":"Journal of Biological Chemistry"},{"key":"ref39","first-page":"339","article-title":"The interpretation of near-ultraviolet circular dichroism","volume":"61","author":"PC Khan","year":"1979"},{"issue":"6","key":"ref40","first-page":"1073","article-title":"Studies of flavine-protein interaction in flavoproteins using protein fluorescence and circular dichroism","volume":"11","author":"JA D'Anna","year":"1972"},{"key":"ref41","first-page":"311","article-title":"<italic>Protein structure<\/italic>: <italic>A practical Apporoach<\/italic>","author":"CN Pace","year":"1989"},{"issue":"8","key":"ref42","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1021\/bi026967s","article-title":"Mechanism of flavin mononucleotide cofactor binding to the Desulfovibrio vulgaris flavodoxin. 1. Kinetic evidence for cooperative effects associated with the binding of inorganic phosphate and the 5\u00b4-phosphate moiety of the cofactor","volume":"42","author":"TA Murray","year":"2003","journal-title":"Biochemistry"},{"issue":"4","key":"ref43","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1016\/j.jmb.2010.05.050","article-title":"Design and Structure of an Equilibrium Protein Folding Intermediate: A Hint into Dynamical Regions of Proteins","volume":"400","author":"S Ayuso-Tejedor","year":"2010","journal-title":"Journal of Molecular Biology"},{"issue":"45","key":"ref44","doi-asserted-by":"crossref","first-page":"47184","DOI":"10.1074\/jbc.M405791200","article-title":"The Long and Short Flavodoxins: II. The role of the differentiating loop in apoflavodoxin stability and folding mechanism","volume":"279","author":"J L\u00f3pez-Llano","year":"2004","journal-title":"Journal of Biological Chemistry"},{"issue":"1","key":"ref45","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.jmb.2004.09.047","article-title":"Do Proteins Always Benefit from a Stability Increase? Relevant and Residual Stabilisation in a Three-state Protein by Charge Optimisation","volume":"344","author":"LA Campos","year":"2004","journal-title":"Journal of Molecular Biology"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"9129","DOI":"10.1038\/srep09129","article-title":"Rational stabilization of complex proteins: a divide and combine approach","volume":"5","author":"E Lamazares","year":"2015","journal-title":"Scientific Reports"},{"issue":"46","key":"ref47","doi-asserted-by":"crossref","first-page":"35454","DOI":"10.1074\/jbc.M607336200","article-title":"Solution Structures and Backbone Dynamics of a Flavodoxin MioC from Escherichia coli in both Apo- and Holo-forms: IMPLICATIONS FOR COFACTOR BINDING AND ELECTRON TRANSFER","volume":"281","author":"Y Hu","year":"2006","journal-title":"Journal of Biological Chemistry"},{"issue":"6","key":"ref48","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1093\/bioinformatics\/16.6.566","article-title":"DaliLite workbench for protein structure comparison","volume":"16","author":"L Holm","year":"2000","journal-title":"Bioinformatics"},{"issue":"4","key":"ref49","first-page":"329","article-title":"Closure of a tyrosine\/tryptophan aromatic gate leads to a compact fold in apo flavodoxin","volume":"3","author":"CG Genzor","year":"1996"},{"issue":"8","key":"ref50","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1093\/embo-reports\/kvf152","article-title":"New approaches towards the identification of antibiotic and vaccine targets in Streptococcus pneumoniae","volume":"3","author":"AM Di Guilmi","year":"2002","journal-title":"EMBO Reports"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/2047-2994-3-16","article-title":"Attributable healthcare utilization and cost of pneumonia due to drug-resistant streptococcus pneumonia: a cost analysis","volume":"3","author":"CA Reynolds","year":"2014","journal-title":"Antimicrobial Resistance and Infection Control"},{"issue":"1","key":"ref52","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1021\/bi00777a019","article-title":"Chemical and physical characterization of the Shethna flavoprotein and apoprotein and kinetics and thermodynamics of flavin analog binding to the apoprotein","volume":"10","author":"DE Edmondson","year":"1971","journal-title":"Biochemistry"},{"issue":"3","key":"ref53","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1093\/protein\/14.3.173","article-title":"Stabilization of apoflavodoxin by replacing hydrogen-bonded charged Asp or Glu residues by the neutral isosteric Asn or Gln","volume":"14","author":"MP Ir\u00fan","year":"2001","journal-title":"Protein Engineering"},{"issue":"1\u20132","key":"ref54","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.abb.2012.10.014","article-title":"The stability of 2-state, 3-state and more-state proteins from simple spectroscopic techniques\u2026 plus the structure of the equilibrium intermediates at the same time","volume":"531","author":"J Sancho","year":"2013","journal-title":"Archives of Biochemistry and Biophysics"},{"issue":"3","key":"ref55","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/0022-2836(74)90188-0","article-title":"A thermodynamic approach to the problem of stabilization of globular protein structure: A calorimetric study","volume":"86","author":"PL Privalov","year":"1974","journal-title":"Journal of Molecular Biology"},{"key":"ref56","first-page":"287","article-title":"<italic>Protein-Ligand Interactions<\/italic>: <italic>hydrodynamics and calorimetry<\/italic>","author":"A Cooper","year":"2000"},{"issue":"Pt 1","key":"ref57","first-page":"22","article-title":"Molecular replacement with MOLREP","volume":"66","author":"A Vagin","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"issue":"Pt 4","key":"ref58","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1107\/S0907444999000839","article-title":"Automated MAD and MIR structure solution","volume":"55","author":"TC Terwilliger","year":"1999","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"issue":"Pt 8","key":"ref59","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1107\/S0907444900005072","article-title":"Maximum-likelihood density modification","volume":"56","author":"TC Terwilliger","year":"2000","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"issue":"Pt 11","key":"ref60","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1107\/S0907444902016657","article-title":"PHENIX: building new software for automated crystallographic structure determination","volume":"58","author":"PD Adams","year":"2002","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"issue":"Pt 12 Pt 1","key":"ref61","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1107\/S0907444904019158","article-title":"Coot: model-building tools for molecular graphics","volume":"60","author":"P Emsley","year":"2004","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"issue":"Pt 3","key":"ref62","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1107\/S0907444996012255","article-title":"Refinement of macromolecular structures by the maximum-likelihood method","volume":"53","author":"GN Murshudov","year":"1997","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"issue":"2","key":"ref63","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1107\/S0021889892009944","article-title":"PROCHECK: a program to check the stereochemical quality of protein structures","volume":"26","author":"RA Laskowski","year":"1993","journal-title":"Journal of Applied Crystallography"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0161020","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T17:58:37Z","timestamp":1657303117000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0161020"}},"subtitle":[],"editor":[{"given":"Bostjan","family":"Kobe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,9,20]]},"references-count":63,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2016,9,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0161020","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,9,20]]}}}