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Structural studies of BpeB and BpeF have identified a hydrophilic patch in their substrate\u2010binding pocket. To investigate the relationship between this hydrophilic patch and substrate specificity, mutant analyses were performed using an\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    recombinant expression system. Drug susceptibility tests of BpeB and BpeF mutants showed up to a 64\u2010fold increase in susceptibility compared with the wild type. Growth curve analyses revealed that BpeB mutants exhibited increased resistance to aminoglycosides, which are not transported by the wild type. These findings suggest that the hydrophilic patches in the substrate\u2010binding pockets of BpeB and BpeF are involved in the substrate specificity.\n                  <\/jats:p>","DOI":"10.1002\/1873-3468.70248","type":"journal-article","created":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T11:38:42Z","timestamp":1765712322000},"page":"537-549","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Substrate specificity of\n                    <i>Burkholderia pseudomallei<\/i>\n                    multidrug transporters is influenced by the hydrophilic patch in the substrate\u2010binding pocket"],"prefix":"10.1002","volume":"600","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7633-9308","authenticated-orcid":false,"given":"Ui","family":"Okada","sequence":"first","affiliation":[{"name":"Department of Life Science and Technology Institute of Science Tokyo  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5553-7663","authenticated-orcid":false,"given":"Satoshi","family":"Murakami","sequence":"additional","affiliation":[{"name":"Department of Life Science and Technology Institute of Science Tokyo  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1385"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.12.116"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2022.2139063"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prrv.2023.11.002"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.18.2.383-416.2005"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.64.4.672-693.2000"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2021.167005"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2015.00327"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.13929"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.14239"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.001438"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13205"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.24905"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403302101"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2015.00305"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.3.465"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01842-13"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000519"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00010-17"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00438-024-02105-w"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.4.1128-1135.2004"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01803-09"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00440-06"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0016892"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2215072120"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2017.09.018"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1128\/jb.177.14.4121-4130.1995"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1107\/S2053230X18013547"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.35.1.1"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10641"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05076"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2008.06.007"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.03383-22"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.03826-24"},{"key":"e_1_2_9_36_1","doi-asserted-by":"crossref","unstructured":"LawrenceR AtharM UddinMR AdamsC SousaJS DurrantO LellmanS SuttonL KeevilCW PatelNet\u00a0al. 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