65271 20201130083155.0 doi 10.3390/molecules23010029 sideral 104238 ART-2018-104238 eng (orcid)0000-0001-9047-0046 Martínez-Júlvez, M. Universidad de Zaragoza Identification of inhibitors targeting ferredoxin-NADP+ reductase from the xanthomonas citri subsp. Citri phytopathogenic bacteria 2018 Access copy available to the general public Unrestricted Ferredoxin-NADP(H) reductases (FNRs) deliver NADPH or low potential one-electron donors to redox-based metabolism in plastids and bacteria. Xanthomonas citri subsp. citri (Xcc) is a Gram-negative bacterium responsible for citrus canker disease that affects commercial citrus crops worldwide. The Xcc fpr gene encodes a bacterial type FNR (XccFPR) that contributes to the bacterial response to oxidative stress conditions, usually found during plant colonization. Therefore, XccFPR is relevant for the pathogen survival and its inhibition might represent a strategy to treat citrus canker. Because of mechanistic and structural differences from plastidic FNRs, XccFPR is also a potential antibacterial target. We have optimized an activity-based high-throughput screening (HTS) assay that identifies XccFPR inhibitors. We selected 43 hits from a chemical library and narrowed them down to the four most promising inhibitors. The antimicrobial effect of these compounds was evaluated on Xcc cultures, finding one with antimicrobial properties. Based on the functional groups of this compound and their geometric arrangement, we identified another three XccFPR inhibitors. Inhibition mechanisms and constants were determined for these four XccFPR inhibitors. Their specificity was also evaluated by studying their effect on the plastidic Anabaena PCC 7119 FNR, finding differences that can become interesting tools to discover Xcc antimicrobials. info:eu-repo/grantAgreement/ES/DGA/B18 info:eu-repo/grantAgreement/ES/MINECO/BFU2016-78232-P info:eu-repo/grantAgreement/ES/MINECO/BIO2016-75183-P info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 3.06 2018 CHEMISTRY, MULTIDISCIPLINARY 67 / 172 = 0.39 2018 Q2 T2 BIOCHEMISTRY & MOLECULAR BIOLOGY 133 / 294 = 0.452 2018 Q2 T2 0.757 2018 Analytical Chemistry 2018 Q1 Chemistry (miscellaneous) 2018 Q1 Drug Discovery 2018 Q1 Physical and Theoretical Chemistry 2018 Q1 Molecular Medicine 2018 Q1 Organic Chemistry 2018 Q1 Pharmaceutical Science 2018 Q1 Medicine (miscellaneous) 2018 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion (orcid)0000-0003-4010-849X Goñi, G. Pérez-Amigot, D. Laplaza, R. Ionescu, I.A. Petrocelli, S. Tondo, M.L. (orcid)0000-0002-2879-9200 Sancho, J. Universidad de Zaragoza Orellano, E.G. (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. 23, 1 (2018), 29 [15 pp] Molecules Molecules 1420-3049 3840426 http://zaguan.unizar.es/record/65271/files/texto_completo.pdf Versión publicada 104731 http://zaguan.unizar.es/record/65271/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:65271 articulos driver 2020-11-30-07:57:24 ARTICLE