{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T19:51:53Z","timestamp":1791834713538,"version":"4.3.4"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,5,31]],"date-time":"2018-05-31T00:00:00Z","timestamp":1527724800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007847","name":"Natural Science Foundation of Jilin Province","doi-asserted-by":"publisher","award":["No. 20180101276JC"],"award-info":[{"award-number":["No. 20180101276JC"]}],"id":[{"id":"10.13039\/100007847","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:p>The antibiotic resistance (<jats:styled-content style=\"fixed-case\">ARE<\/jats:styled-content>) subfamily of <jats:styled-content style=\"fixed-case\">ABC<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>\u2010binding cassette) proteins confers resistance to a variety of clinically important ribosome\u2010targeting antibiotics and plays an important role in infections caused by pathogenic bacteria. However, inhibitors of <jats:styled-content style=\"fixed-case\">ARE<\/jats:styled-content> proteins have rarely been reported. Here, OptrA, a new member of the <jats:styled-content style=\"fixed-case\">ARE<\/jats:styled-content> proteins, was used to study inhibitors of these types of proteins. We first confirmed that destroying the catalytic activity of OptrA could restore the sensitivity of host cells to antibiotics. Then, fragment\u2010based screening, a drug screening method, was used to screen for inhibitors of OptrA. The competitive saturation transfer difference experiments, docking, and molecular dynamics were used to determine the binding sites and mode of interactions between OptrA and fragment screening hits. In this study, we first find a novel and specific inhibitor of OptrA (<jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content>1), which suppressed the <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>ase activity of OptrA in vitro by 30%. A hydrogen bond formed between the 8\u2010position phenylcyclic cyano group in <jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content>1 and the amino acid residue Lys\u2010271 allows <jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content>1 to form a stable complex with OptrA protein. These findings provide a theoretical basis for the further optimization of the inhibitor structure to obtain inhibitors with higher efficiencies.<\/jats:p>","DOI":"10.1111\/cbdd.13311","type":"journal-article","created":{"date-parts":[[2018,4,19]],"date-time":"2018-04-19T14:36:01Z","timestamp":1524148561000},"page":"1458-1467","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A novel inhibitor of the new antibiotic resistance protein OptrA"],"prefix":"10.1111","volume":"92","author":[{"given":"Xiaobo","family":"Zhong","sequence":"first","affiliation":[{"name":"College of Animal Science Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Xiang","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology Jilin Agricultural University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiedong","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Animal Science Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zhong","sequence":"additional","affiliation":[{"name":"College of Animal Science Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Ming","sequence":"additional","affiliation":[{"name":"College of Animal Science Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linyan","family":"Nie","sequence":"additional","affiliation":[{"name":"College of Animal Science Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengjiao","family":"Cao","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology Jilin Agricultural University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bangbang","family":"Li","sequence":"additional","affiliation":[{"name":"College of Animal Science Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Cao","sequence":"additional","affiliation":[{"name":"College of Animal Science Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Mu","sequence":"additional","affiliation":[{"name":"College of Animal Science Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Ruan","sequence":"additional","affiliation":[{"name":"Hefei National Laboratory for Physical Science at the Microscale School of Life Sciences University of Science and Technology of China  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3963-0742","authenticated-orcid":false,"given":"Lin","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Zoonosis Research Ministry of Education Institute of Zoonosis College of Veterinary Medicine Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dacheng","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Animal Science Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,5,31]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01975-15"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkv116"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2015.08.007"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkw016"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkv438"},{"key":"e_1_2_8_7_1","first-page":"678","volume":"72","author":"Cavaco L. 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