{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T10:28:18Z","timestamp":1789727298553,"version":"4.0.1"},"reference-count":62,"publisher":"The Royal Society","issue":"9","license":[{"start":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:00:00Z","timestamp":1472688000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"funder":[{"DOI":"10.13039\/100000774","name":"Defense Threat Reduction Agency","doi-asserted-by":"publisher","award":["HDTRA1-07-C-0005"],"award-info":[{"award-number":["HDTRA1-07-C-0005"]}],"id":[{"id":"10.13039\/100000774","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/H00405X\/1"],"award-info":[{"award-number":["BB\/H00405X\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/K10069\/1"],"award-info":[{"award-number":["BB\/K10069\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["Open Biol."],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:p>\n            As part of a programme of synthesizing and investigating the biological properties of new fluoroquinolone antibacterials and their targeting of topoisomerase IV from\n            <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n            , we have solved the X-ray structure of the complexes of two new 7,8-bridged fluoroquinolones (with restricted C7 group rotation favouring tight binding) in complex with the topoisomerase IV from\n            <jats:italic>S. pneumoniae<\/jats:italic>\n            and an 18-base-pair DNA binding site\u2014the E-site\u2014found by our DNA mapping studies to bind drug strongly in the presence of topoisomerase IV (Leo\n            <jats:italic>et al.<\/jats:italic>\n            2005\n            <jats:italic>J. Biol. Chem.<\/jats:italic>\n            <jats:bold>280<\/jats:bold>\n            , 14 252\u201314 263,\n            <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/dx.doi.org\/10.1074\/jbc.M500156200\">doi:10.1074\/jbc.M500156200<\/jats:ext-link>\n            ). Although the degree of antibiotic resistance towards fluoroquinolones is much lower than that of \u03b2-lactams and a range of ribosome-bound antibiotics, there is a pressing need to increase the diversity of members of this successful clinically used class of drugs. The quinolone moiety of the new 7,8-bridged agents ACHN-245 and ACHN-454 binds similarly to that of clinafloxocin, levofloxacin, moxifloxacin and trovofloxacin but the cyclic scaffold offers the possibility of chemical modification to produce interactions with other topoisomerase residues at the active site.\n          <\/jats:p>","DOI":"10.1098\/rsob.160157","type":"journal-article","created":{"date-parts":[[2016,9,22]],"date-time":"2016-09-22T19:17:22Z","timestamp":1474571842000},"page":"160157","update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":30,"title":["Exploring the active site of the\n            <i>Streptococcus pneumoniae<\/i>\n            topoisomerase IV\u2013DNA cleavage complex with novel 7,8-bridged fluoroquinolones"],"prefix":"10.1098","volume":"6","author":[{"given":"Ivan","family":"Laponogov","sequence":"first","affiliation":[{"name":"Randall Division of Cell and Molecular Biophysics, King's College, Guy's Campus, London Bridge, London SE1 1UL, UK"},{"name":"Molecular and Clinical Sciences Research Institute, St George's, University of London, Cranmer Terrace, London SW17 0RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Su","family":"Pan","sequence":"additional","affiliation":[{"name":"Molecular and Clinical Sciences Research Institute, St George's, University of London, Cranmer Terrace, London SW17 0RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis A.","family":"Veselkov","sequence":"additional","affiliation":[{"name":"Randall Division of Cell and Molecular Biophysics, King's College, Guy's Campus, London Bridge, London SE1 1UL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan T.","family":"Cirz","sequence":"additional","affiliation":[{"name":"Achaogen, 7000 Shoreline Ct. No. 371, San Francisco, CA 94080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan","family":"Wagman","sequence":"additional","affiliation":[{"name":"Achaogen, 7000 Shoreline Ct. No. 371, San Francisco, CA 94080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz E.","family":"Moser","sequence":"additional","affiliation":[{"name":"Achaogen, 7000 Shoreline Ct. No. 371, San Francisco, CA 94080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2172-3369","authenticated-orcid":false,"given":"L. Mark","family":"Fisher","sequence":"additional","affiliation":[{"name":"Molecular and Clinical Sciences Research Institute, St George's, University of London, Cranmer Terrace, London SW17 0RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4235-7780","authenticated-orcid":false,"given":"Mark R.","family":"Sanderson","sequence":"additional","affiliation":[{"name":"Randall Division of Cell and Molecular Biophysics, King's College, Guy's Campus, London Bridge, London SE1 1UL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2016,9]]},"reference":[{"key":"e_1_3_4_2_2","first-page":"402","article-title":"Changes in antimicrobial resistance, serotypes and genotypes in","volume":"16","author":"Li\u00f1ares J","year":"2010","journal-title":"Eur. Soc. Micro. Inf. Dis"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3228"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt749"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1128\/.61.3.377-392.1997","article-title":"DNA gyrase, topoisomerase IV, and the 4-quinolones","volume":"61","author":"Drlica K","year":"1997","journal-title":"Microbiol. Mol. Biol. Rev"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01617-06"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2016.01.006"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt238"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1017\/S003358350800468X"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2608"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2607"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp024"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2012.07.014"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1204117"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt828"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.1604"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011338"},{"key":"e_1_3_4_18_2","first-page":"488","article-title":"Structure of a quinolone-stabilized cleavage complex of topoisomerase IV from Klebsiella pneumoniae and comparison with a related Streptococcus pneumoniae complex","volume":"72","author":"Veselkov DA","year":"2016","journal-title":"Acta Cryst"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04124-14"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep11827"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b00863"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1021\/cb500629k"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09197"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10048"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.529164"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/cb300648v"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1107\/S2053230X15015290"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00113-09"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1525055113"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M500156200"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt696"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.1892"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.5.1129"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.11.3140-3147.2001"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.2.413-419.2002"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2006.09.006"},{"key":"e_1_3_4_37_2","first-page":"125","article-title":"XDS","volume":"66","author":"Kabsch W","year":"2010","journal-title":"Acta Cryst"},{"key":"e_1_3_4_38_2","first-page":"133","article-title":"Integration, scaling, space-group assignment and post-refinement","volume":"66","author":"Kabsch W","year":"2010","journal-title":"Acta Cryst"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889807021206"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444910045749"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444902016657"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444909052925"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444904019158"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444910007493"},{"key":"e_1_3_4_45_2","volume-title":"The PyMOL molecular graphics system","author":"DeLano WL","year":"2008"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201405820"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889892009944"},{"key":"e_1_3_4_48_2","unstructured":"Wagman AS et al. 2009 Achaogen Inc. USA. PCT Int. Appl. WO 2009137130 A2 20091112 322p."},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0000301"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003201"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-440X(99)00057-3"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2388"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1525047113"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.178.14.4060-4069.1996"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.10.2321"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.23.8924"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7528445"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.177.22.6321-6329.1995"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/34593"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2006.03.013"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.11.2810"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1097\/SMJ.0b013e3181fd7d5a"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.2174\/1568026613666131113153251"}],"container-title":["Open Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rsob.160157","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/full-xml\/10.1098\/rsob.160157","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rsob.160157","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T00:27:44Z","timestamp":1613608064000},"score":1,"resource":{"primary":{"URL":"https:\/\/royalsocietypublishing.org\/doi\/10.1098\/rsob.160157"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,9]]},"references-count":62,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2016,9]]}},"alternative-id":["10.1098\/rsob.160157"],"URL":"https:\/\/doi.org\/10.1098\/rsob.160157","relation":{},"ISSN":["2046-2441"],"issn-type":[{"value":"2046-2441","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,9]]},"assertion":[{"value":"2016-05-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-08-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-09-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}