{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:47:48Z","timestamp":1793148468728,"version":"4.5.0"},"reference-count":54,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"Division of Intramural Research of the National Institute of Environmental Health Sciences, National Institutes of Health","doi-asserted-by":"publisher","award":["ZIA ES103328"],"award-info":[{"award-number":["ZIA ES103328"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"Division of Intramural Research of the National Institute of Environmental Health Sciences, National Institutes of Health","doi-asserted-by":"publisher","award":["ZIC ES102645"],"award-info":[{"award-number":["ZIC ES102645"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"Division of Intramural Research of the National Institute of Environmental Health Sciences, National Institutes of Health","doi-asserted-by":"publisher","award":["ZIC ES103005"],"award-info":[{"award-number":["ZIC ES103005"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"Division of Intramural Research of the National Institute of Environmental Health Sciences, National Institutes of Health","doi-asserted-by":"publisher","award":["ZIC ES043010"],"award-info":[{"award-number":["ZIC ES043010"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institutes of Health, and funding from the Georgia Research Alliance","award":["S10_RR25528"],"award-info":[{"award-number":["S10_RR25528"]}]},{"name":"National Institutes of Health, and funding from the Georgia Research Alliance","award":["S10_RR028976"],"award-info":[{"award-number":["S10_RR028976"]}]},{"name":"National Institutes of Health, and funding from the Georgia Research Alliance","award":["S10_OD027000"],"award-info":[{"award-number":["S10_OD027000"]}]},{"name":"Advanced Photon Source","award":["DE-AC02-06CH11357"],"award-info":[{"award-number":["DE-AC02-06CH11357"]}]},{"DOI":"10.13039\/100018075","name":"Advanced Light Source","doi-asserted-by":"crossref","award":["DE-AC02-05CH11231"],"award-info":[{"award-number":["DE-AC02-05CH11231"]}],"id":[{"id":"10.13039\/100018075","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Howard Hughes Medical Institute, Participating Research Team members, and the National Institutes of Health, National Institute of General Medical Sciences","award":["P30 GM124169"],"award-info":[{"award-number":["P30 GM124169"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Pseudomonas aeruginosa is considered a priority pathogen by the World Health Organization due to its resistance to antibiotics. Isolates resistant to ciprofloxacin (CPFX), a bactericide commonly used against P. aeruginosa, usually carry the mutations T83I or D87N in the GyrA subunit of the DNA gyrase. Yet, the molecular mechanisms by which these mutations confer CPFX-resistance to P. aeruginosa are unknown. Here we solved the crystal structure of the P. aeruginosa gyrase catalytic cleavage core and used it to carry out molecular dynamic (MD) simulations of CPFX-gyrase binding in the wild-type as well as the T83I and the D87N mutant systems. Our results show that DNA plays the most prominent stabilizing role once CPFX is bound, with relatively minor contributions from Thr83 or Asp87. Interestingly, we found a solvent cavity adjacent to these residues that may provide CPFX access to the active site. Interaction energy analysis using Umbrella Sampling indicates that Thr83 and Asp87 may influence CPFX trajectory during binding. In the mutant systems, the repulsive potential increases at the cavity site, which may hinder CPFX accessing the binding site. These results shed light on P. aeruginosa resistance to CPFX and may help provide a methodology to identify new therapeutic agents to target fluoroquinolone resistant bacteria.<\/jats:p>","DOI":"10.3390\/biom16020318","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T12:59:16Z","timestamp":1771419556000},"page":"318","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Structural and Computational Analysis of Pseudomonas aeruginosa DNA Gyrase Reveals Molecular Characteristics That May Contribute to Ciprofloxacin Resistance"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0823-1631","authenticated-orcid":false,"given":"Lalith","family":"Perera","sequence":"first","affiliation":[{"name":"Genomic Integrity & Structural Biology Laboratory, NIEHS, Durham, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9796-9341","authenticated-orcid":false,"given":"Libertad","family":"Garc\u00eda-Villada","sequence":"additional","affiliation":[{"name":"Genomic Integrity & Structural Biology Laboratory, NIEHS, Durham, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6263-4186","authenticated-orcid":false,"given":"Andrea M.","family":"Kaminski","sequence":"additional","affiliation":[{"name":"Genomic Integrity & Structural Biology Laboratory, NIEHS, Durham, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7141-6308","authenticated-orcid":false,"given":"Natalya","family":"Degtyareva","sequence":"additional","affiliation":[{"name":"Genomic Integrity & Structural Biology Laboratory, NIEHS, Durham, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4488-4077","authenticated-orcid":false,"given":"Lars C.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Genomic Integrity & Structural Biology Laboratory, NIEHS, Durham, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3195-3413","authenticated-orcid":false,"given":"Paul W.","family":"Doetsch","sequence":"additional","affiliation":[{"name":"Genomic Integrity & Structural Biology Laboratory, NIEHS, Durham, NC 27709, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1128\/CMR.00040-09","article-title":"Antibacterial-resistant Pseudomonas aeruginosa: Clinical impact and complex regulation of chromosomally encoded resistance mechanisms","volume":"22","author":"Lister","year":"2009","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Garcia-Clemente, M., de la Rosa, D., Maiz, L., Giron, R., Blanco, M., Olveira, C., Canton, R., and Martinez-Garcia, M.A. (2020). Impact of Pseudomonas aeruginosa Infection on Patients with Chronic Inflammatory Airway Diseases. J. Clin. Med., 9.","DOI":"10.3390\/jcm9123800"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/s41579-020-00477-5","article-title":"Pseudomonas aeruginosa adaptation and evolution in patients with cystic fibrosis","volume":"19","author":"Rossi","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Morita, Y., Tomida, J., and Kawamura, Y. (2014). Responses of Pseudomonas aeruginosa to antimicrobials. Front. Microbiol., 4.","DOI":"10.3389\/fmicb.2013.00422"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.2217\/fmb.15.48","article-title":"Pseudomonas aeruginosa: Arsenal of resistance mechanisms, decades of changing resistance profiles, and future antimicrobial therapies","volume":"10","author":"Webster","year":"2015","journal-title":"Future Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e01603-15","DOI":"10.1128\/mBio.01603-15","article-title":"Intrinsic Antimicrobial Resistance Determinants in the Superbug Pseudomonas aeruginosa","volume":"6","author":"Murray","year":"2015","journal-title":"MBio"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"100640","DOI":"10.1016\/j.drup.2019.07.002","article-title":"Antibiotic resistance in Pseudomonas aeruginosa\u2014Mechanisms, epidemiology and evolution","volume":"44","author":"Botelho","year":"2019","journal-title":"Drug Resist. Updates"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8598","DOI":"10.1038\/s41598-024-59188-z","article-title":"A role for the stringent response in ciprofloxacin resistance in Pseudomonas aeruginosa","volume":"14","author":"Degtyareva","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1080\/1040841X.2024.2313024","article-title":"Antibiotic resistance: A global crisis, problems and solutions","volume":"50","author":"Aggarwal","year":"2024","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1099\/jmm.0.000873","article-title":"Mechanisms of ciprofloxacin resistance in Pseudomonas aeruginosa: New approaches to an old problem","volume":"68","author":"Rehman","year":"2019","journal-title":"J. Med. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1021\/bi5000564","article-title":"Mechanism of quinolone action and resistance","volume":"53","author":"Aldred","year":"2014","journal-title":"Biochemistry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/nyas.12830","article-title":"Mechanisms of drug resistance: Quinolone resistance","volume":"1354","author":"Hooper","year":"2015","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"a025320","DOI":"10.1101\/cshperspect.a025320","article-title":"Topoisomerase Inhibitors: Fluoroquinolone Mechanisms of Action and Resistance","volume":"6","author":"Hooper","year":"2016","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Bush, N.G., Diez-Santos, I., Abbott, L.R., and Maxwell, A. (2020). Quinolones: Mechanism, Lethality and Their Contributions to Antibiotic Resistance. Molecules, 25.","DOI":"10.3390\/molecules25235662"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Sada, M., Kimura, H., Nagasawa, N., Akagawa, M., Okayama, K., Shirai, T., Sunagawa, S., Kimura, R., Saraya, T., and Ishii, H. (2022). Molecular Evolution of the Pseudomonas aeruginosa DNA Gyrase gyrA Gene. Microorganisms, 10.","DOI":"10.3390\/microorganisms10081660"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Stanger, F.V., Dehio, C., and Schirmer, T. (2014). Structure of the N-terminal Gyrase B fragment in complex with ADP\u22c5Pi reveals rigid-body motion induced by ATP hydrolysis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0107289"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1016\/j.jmb.2016.03.016","article-title":"Structural Dynamics and Mechanochemical Coupling in DNA Gyrase","volume":"428","author":"Basu","year":"2016","journal-title":"J. Mol. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Spencer, A.C., and Panda, S.S. (2023). DNA Gyrase as a Target for Quinolones. Biomedicines, 11.","DOI":"10.3390\/biomedicines11020371"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"10048","DOI":"10.1038\/ncomms10048","article-title":"Structural basis of DNA gyrase inhibition by antibacterial QPT-1, anticancer drug etoposide and moxifloxacin","volume":"6","author":"Chan","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_20","first-page":"377","article-title":"DNA gyrase, topoisomerase IV, and the 4-quinolones","volume":"61","author":"Drlica","year":"1997","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1002\/cbic.200800041","article-title":"Mechanism of binding of fluoroquinolones to the quinolone resistance-determining region of DNA gyrase: Towards an understanding of the molecular basis of quinolone resistance","volume":"9","author":"Madurga","year":"2008","journal-title":"Chembiochem"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1038\/nature09197","article-title":"Type IIA topoisomerase inhibition by a new class of antibacterial agents","volume":"466","author":"Bax","year":"2010","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1038\/nsmb.1892","article-title":"Structural basis of quinolone inhibition of type IIA topoisomerases and target-mediated resistance","volume":"17","author":"Wohlkonig","year":"2010","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1073\/pnas.1525047113","article-title":"Crystal structure and stability of gyrase-fluoroquinolone cleaved complexes from Mycobacterium tuberculosis","volume":"113","author":"Blower","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1080\/07391102.2016.1277784","article-title":"Dynamics of fluoroquinolones induced resistance in DNA gyrase of Mycobacterium tuberculosis","volume":"36","author":"Pandey","year":"2018","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"104244","DOI":"10.1016\/j.bioorg.2020.104244","article-title":"Structure based drug discovery and in vitro activity testing for DNA gyrase inhibitors of Salmonella enterica serovar Typhi","volume":"104","author":"Sharma","year":"2020","journal-title":"Bioorg. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Fekadu, M., Zeleke, D., Abdi, B., Guttula, A., Eswaramoorthy, R., and Melaku, Y. (2022). Synthesis, in silico molecular docking analysis, pharmacokinetic properties and evaluation of antibacterial and antioxidant activities of fluoroquinolines. BMC Chem., 16.","DOI":"10.1186\/s13065-022-00795-0"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1080\/08927022.2024.2332453","article-title":"Molecular dynamics simulation guided analysis of the interaction between delafloxacin and Staphylococcus aureus gyrase mutants","volume":"50","year":"2024","journal-title":"Mol. Simul."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1038\/42294","article-title":"Crystal structure of the breakage-reunion domain of DNA gyrase","volume":"388","author":"Jackson","year":"1997","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4935","DOI":"10.1038\/s41467-019-12914-y","article-title":"Cryo-EM structure of the complete E. coli DNA gyrase nucleoprotein complex","volume":"10","author":"Lotz","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1021\/acsinfecdis.8b00315","article-title":"Mechanistic and Structural Basis for the Actions of the Antibacterial Gepotidacin against Staphylococcus aureus Gyrase","volume":"5","author":"Gibson","year":"2019","journal-title":"ACS Infect. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7815","DOI":"10.1093\/nar\/gkt560","article-title":"Structural insight into negative DNA supercoiling by DNA gyrase, a bacterial type 2A DNA topoisomerase","volume":"41","author":"Papillon","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/nsmb.1604","article-title":"Structural insight into the quinolone-DNA cleavage complex of type IIA topoisomerases","volume":"16","author":"Laponogov","year":"2009","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e41215","DOI":"10.7554\/eLife.41215","article-title":"CryoEM structures of open dimers of gyrase A in complex with DNA illuminate mechanism of strand passage","volume":"7","author":"Soczek","year":"2018","journal-title":"ELife"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1007\/s12033-024-01076-y","article-title":"Molecular Analysis of Pseudomonas aeruginosa Isolates with Mutant gyrA Gene and Development of a New Ciprofloxacin Derivative for Antimicrobial Therapy","volume":"67","author":"Alabdali","year":"2025","journal-title":"Mol. Biotechnol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/nsmb.2766","article-title":"Sustained active site rigidity during synthesis by human DNA polymerase mu","volume":"21","author":"Moon","year":"2014","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1107\/S0907444906019949","article-title":"HKL-3000: The integration of data reduction and structure solution\u2014From diffraction images to an initial model in minutes","volume":"62","author":"Minor","year":"2006","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1107\/S0907444906045975","article-title":"Solving structures of protein complexes by molecular replacement with Phaser","volume":"63","author":"McCoy","year":"2007","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"7830","DOI":"10.1093\/nar\/gkq665","article-title":"A domain insertion in Escherichia coli GyrB adopts a novel fold that plays a critical role in gyrase function","volume":"38","author":"Schoeffler","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1107\/S0907444904019158","article-title":"Coot: Model-building tools for molecular graphics","volume":"60","author":"Emsley","year":"2004","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1107\/S0907444910007493","article-title":"Features and development of Coot","volume":"66","author":"Emsley","year":"2010","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1107\/S0907444909052925","article-title":"PHENIX: A comprehensive Python-based system for macromolecular structure solution","volume":"66","author":"Adams","year":"2010","journal-title":"Acta Crystallogr. D"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1107\/S0907444909042073","article-title":"MolProbity: All-atom structure validation for macromolecular crystallography","volume":"66","author":"Chen","year":"2010","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"ref_44","unstructured":"Nitiss, J.L. (2001). Topoisomerase assays. Curr. Protoc. Pharmacol., Chapter 3."},{"key":"ref_45","unstructured":"\u0160ali, A., Webb, B., Madhusudhan, M.S., Shen, M.-Y., Dong, G., Marti-Renom, M.A., Eswar, N., Alber, F., Topf, M., and Oliva, B. (2025, December 23). MODELLER (Release 10.2). Available online: https:\/\/salilab.org\/modeller\/10.2\/manual.pdf."},{"key":"ref_46","unstructured":"Case, D.A., Aktulga, H.M., Belfon, K., Ben-Shalom, I.Y., Berryman, J.T., Brozell, S.R., Cerutti, D.S., Cheatham, T.E., Cisneros, G.A., and Cruzeiro, V.W.D. (2022). Amber 2022, University of California."},{"key":"ref_47","unstructured":"Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Scalmani, G., Barone, V., Petersson, G.A., and Nakatsuji, H. (2016). Gaussian 16 Rev. C.01, Gaussian Inc.. Available online: https:\/\/gaussian.com\/citation_b01\/."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3084","DOI":"10.1021\/ct400341p","article-title":"PTRAJ and CPPTRAJ: Software for Processing and Analysis of Molecular Dynamics Trajectory Data","volume":"9","author":"Roe","year":"2013","journal-title":"J. Chem. Theory Comput."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3314","DOI":"10.1021\/ct300418h","article-title":"MMPBSA.py: An Efficient Program for End-State Free Energy Calculations","volume":"8","author":"Miller","year":"2012","journal-title":"J. Chem. Theory Comput."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014A visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e2407398121","DOI":"10.1073\/pnas.2407398121","article-title":"Structural basis of chiral wrap and T-segment capture by Escherichia coli DNA gyrase","volume":"121","author":"Michalczyk","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Elfadadny, A., Ragab, R.F., AlHarbi, M., Badshah, F., Ib\u00e1\u00f1ez-Arancibia, E., Farag, A., Hendawy, A.O., De los R\u00edos-Escalante, P.R., Aboubakr, M., and Zakai, S.A. (2024). Antimicrobial resistance of Pseudomonas aeruginosa: Navigating clinical impacts, current resistance trends, and innovations in breaking therapies. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1374466"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Caffrey, A.R., Appaneal, H.J., Liao, J.X., Piehl, E.C., Lopes, V., and Puzniak, L.A. (2022). Treatment Heterogeneity in Pneumonia. Antibiotics, 11.","DOI":"10.3390\/antibiotics11081033"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1093\/bfgp\/elac029","article-title":"Targeting novel sites in DNA gyrase for development of anti-microbials","volume":"22","author":"Salman","year":"2023","journal-title":"Brief. Funct. Genom."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/2\/318\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T05:15:15Z","timestamp":1771564515000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/2\/318"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,18]]},"references-count":54,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["biom16020318"],"URL":"https:\/\/doi.org\/10.3390\/biom16020318","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,18]]}}}