{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T14:48:54Z","timestamp":1775486934690,"version":"3.50.1"},"reference-count":36,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:00:00Z","timestamp":1675296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"UExplore Undergraduate Research Program at the University of Evansville","doi-asserted-by":"publisher","award":["T32 GM008365"],"award-info":[{"award-number":["T32 GM008365"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"UExplore Undergraduate Research Program at the University of Evansville","doi-asserted-by":"publisher","award":["T32 GM008365"],"award-info":[{"award-number":["T32 GM008365"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"UExplore Undergraduate Research Program at the University of Evansville","doi-asserted-by":"publisher","award":["AI87671"],"award-info":[{"award-number":["AI87671"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 GM008365"],"award-info":[{"award-number":["T32 GM008365"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 GM008365"],"award-info":[{"award-number":["T32 GM008365"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI87671"],"award-info":[{"award-number":["AI87671"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Fluoroquinolones are an important class of antibacterials, and rising levels of resistance threaten their clinical efficacy. Gaining a more full understanding of their mechanism of action against their target enzymes\u2014the bacterial type II topoisomerases gyrase and topoisomerase IV\u2014may allow us to rationally design quinolone-based drugs that overcome resistance. As a step toward this goal, we investigated whether the water\u2013metal ion bridge that has been found to mediate the major point of interaction between Escherichia coli topoisomerase IV and Bacillus anthracis topoisomerase IV and gyrase, as well as Mycobacterium tuberculosis gyrase, exists in E. coli gyrase. This is the first investigation of the water\u2013metal ion bridge and its function in a Gram-negative gyrase. Evidence suggests that the water\u2013metal ion bridge does exist in quinolone interactions with this enzyme and, unlike the Gram-positive B. anthracis gyrase, does use both conserved residues (serine and acidic) as bridge anchors. Furthermore, this interaction appears to play a positioning role. These findings raise the possibility that the water\u2013metal ion bridge is a universal point of interaction between quinolones and type II topoisomerases and that it functions primarily as a binding contact in Gram-positive species and primarily as a positioning interaction in Gram-negative species. Future studies will explore this possibility.<\/jats:p>","DOI":"10.3390\/ijms24032879","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T04:55:12Z","timestamp":1675313712000},"page":"2879","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Role of the Water\u2013Metal Ion Bridge in Quinolone Interactions with Escherichia coli Gyrase"],"prefix":"10.3390","volume":"24","author":[{"given":"Hannah E.","family":"Carter","sequence":"first","affiliation":[{"name":"Biology Department, University of Evansville, Evansville, IN 47722, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baylee","family":"Wildman","sequence":"additional","affiliation":[{"name":"Biology Department, University of Evansville, Evansville, IN 47722, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heidi A.","family":"Schwanz","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Experimental Therapeutics, University of Iowa, Iowa City, IA 42232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5371-403X","authenticated-orcid":false,"given":"Robert J.","family":"Kerns","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Experimental Therapeutics, University of Iowa, Iowa City, IA 42232, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katie J.","family":"Aldred","sequence":"additional","affiliation":[{"name":"Biology Department, University of Evansville, Evansville, IN 47722, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1128\/AAC.00665-08","article-title":"Mechanisms accounting for fluoroquinolone resistance in Escherichia coli clinical isolates","volume":"53","author":"Steffen","year":"2009","journal-title":"Antimicrob. 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