{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T10:21:04Z","timestamp":1760782864575},"reference-count":20,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2006,6,15]],"date-time":"2006-06-15T00:00:00Z","timestamp":1150329600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2006,7]]},"abstract":"<jats:p>We report a detailed kinetic investigation of the aminoglycosides neomycin B and neamine as inhibitors of the lethal factor protease from <jats:italic>Bacillus anthracis<\/jats:italic>. Both inhibitors display a mixed\u2010type, noncompetitive kinetic pattern, which suggests the existence of multiple enzyme\u2013inhibitor binding sites or the involvement of multiple structural binding modes at the same site. Quantitative analysis of the ionic strength effects by using the Debye\u2013H\u00fcckel model revealed that the average interionic distance at the point of enzyme\u2013inhibitor attachment is likely to be extremely short, which suggests specific, rather than nonspecific, binding. Only one ion pair seems to be involved in the binding process, which suggests the presence of a single binding site. Combining the results of our substrate competition studies with the ionic strength effects on the apparent inhibition constant, we propose that aminoglycoside inhibitors, such as neomycin B, bind to the lethal factor protease from <jats:italic>B.\u2003anthracis<\/jats:italic> in two different structural orientations. These results have important implications for the rational design of lethal factor protease inhibitors as possible therapeutic agents against anthrax. The strategies and methods we describe are general and can be employed to investigate in depth the mechanism of inhibition by other bioactive compounds.<\/jats:p>","DOI":"10.1111\/j.1742-4658.2006.05316.x","type":"journal-article","created":{"date-parts":[[2006,6,15]],"date-time":"2006-06-15T15:30:28Z","timestamp":1150385428000},"page":"3054-3062","source":"Crossref","is-referenced-by-count":25,"title":["Mixed\u2010type noncompetitive inhibition of anthrax lethal factor protease by aminoglycosides"],"prefix":"10.1111","volume":"273","author":[{"given":"Petr","family":"Kuzmic","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynne","family":"Cregar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sherri Z.","family":"Millis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Goldman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,6,15]]},"reference":[{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5364.734"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja0495359"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200462003"},{"key":"e_1_2_8_5_2","unstructured":"TangC SimoO NagataM JiaoG\u2010S O'MalleyS GoldmanM CregarL NguyenD&HemscheidtT(2004)Guanidinylated neamine analogs inhibit LF with Kiapp of 1.5\u201325.0 \u00b5M. 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