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However, the molecular mechanism of their potential antiprotozoal activity is less well understood. In the present study, we have examined the in\u2005vitro inhibitory activities of some aminoglycosides with a 6\u2032\u2010hydroxy group on ring\u2005I and highlight that one of them, 6\u2032\u2010hydroxysisomicin, exhibits promising activity against a broad range of protozoan parasites. Furthermore, we have conducted X\u2010ray analyses of 6\u2032\u2010hydroxysisomicin bound to the target ribosomal RNA A\u2010sites in order to understand the mechanisms of both its antibacterial and antiprotozoal activities at the molecular level. The unsaturated ring\u2005I of 6\u2032\u2010hydroxysisomicin can directly stack on G1491, which is highly conserved in bacterial and protozoal species, through \u03c0\u2013\u03c0 interaction and fits closer to the guanidine base than the typically saturated and hydroxylated ring\u2005I of other structurally related aminoglycosides. Consequently, the compound adopts a lower energy conformation within the bacterial and protozoal A\u2010sites and makes pseudo pairs to either A or G at position\u20051408. The A\u2010site\u2010selective binding mode strongly suggests that 6\u2032\u2010hydroxysisomicin is a potential lead for the design of next\u2010generation aminoglycosides targeting a wide variety of infectious diseases.<\/jats:p>","DOI":"10.1002\/cmdc.201200579","type":"journal-article","created":{"date-parts":[[2013,2,21]],"date-time":"2013-02-21T17:13:34Z","timestamp":1361466814000},"page":"733-739","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Crystal Structures of a Bioactive 6\u2032\u2010Hydroxy Variant of Sisomicin Bound to the Bacterial and Protozoal Ribosomal Decoding Sites"],"prefix":"10.1002","volume":"8","author":[{"given":"Jiro","family":"Kondo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mai","family":"Koganei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Pablo","family":"Maianti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vu Linh","family":"Ly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Hanessian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,2,21]]},"reference":[{"volume-title":"Aminoglycoside Antibiotics: From Chemical Biology to Drug Discovery","year":"2007","key":"e_1_2_7_1_2"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.16.3.430-450.2003"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.5.1003"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2008.04.015"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.2174\/1568005023342533"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/9781555815615.ch3"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/9780470149676.ch3"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.26.412"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/327389a0"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5291.1367"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.74.061903.155440"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(01)00629-3"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/21.9.2272"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb1271"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.6.5.579"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.7.6.811"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exppara.2006.12.004"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm658"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.17.5.787"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trstmh.2008.09.008"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2010.03.023"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-3-2"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201106084"},{"key":"e_1_2_7_23_3","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201106084"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1039\/c29710000285"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1039\/p19750000814"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm00200a009"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1039\/b925668g"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1039\/c1sc00538c"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1021\/ml300145y"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol2027703"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.081082398"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(02)01452-3"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi020130f"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1086\/515328"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.12.5112-5118.2005"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.4.1489-1496.2006"},{"key":"e_1_2_7_37_2","unstructured":"First WHO report on neglected diseases: Working to Overcome the Global Impact of Neglected Tropical Diseases World Health Organization (WHO) Geneva Switzerland 2010."},{"key":"e_1_2_7_38_2","first-page":"196","volume":"2","author":"Zavitsanou A.","year":"2008","journal-title":"Health Sci. 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