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The low sequence similarity among the members of the large mammalian \u03b2\u2010defensin family suggests that their antimicrobial activity is largely independent of their primary structure. To investigate to what extent these defensins share a similar fold, the structures of the two human \u03b2\u2010defensins, hBD\u20101 and hBD\u20102, as well as those of two novel murine defensins, termed mBD\u20107 and mBD\u20108, were determined by nuclear magnetic resonance spectroscopy. All four defensins investigated share a striking similarity on the level of secondary and tertiary structure including the lack of a distinct hydrophobic core, suggesting that the fold is mainly stabilized by the presence of three disulfide bonds. In addition to the overall shape of the molecules, the ratio of solvent\u2010exposed polar and hydrophobic side chains is also very similar among the four defensins investigated. It is significant that \u03b2\u2010defensins do not exhibit a common pattern of charged and hydrophobic residues on the protein surface and that the \u03b2\u2010defensin\u2010specific fold appears to accommodate a wide range of different amino acids at most sequence positions. In addition to the implications for the mode of biological defensin actions, these findings are of particular interest because \u03b2\u2010defensins have been suggested as lead compounds for the development of novel peptide antibiotics for the therapy of infectious diseases.<\/jats:p>","DOI":"10.1110\/ps.24401","type":"journal-article","created":{"date-parts":[[2009,2,17]],"date-time":"2009-02-17T23:33:33Z","timestamp":1234913613000},"page":"2470-2479","source":"Crossref","is-referenced-by-count":25,"title":["Structure determination of human and murine \u03b2\u2010defensins reveals structural conservation in the absence of significant sequence similarity"],"prefix":"10.1002","volume":"10","author":[{"given":"Finn","family":"Bauer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian","family":"Schweimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enno","family":"Kl\u00fcver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose\u2010Ramon","family":"Conejo\u2010Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolf\u2010Georg","family":"Forssmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"R\u00f6sch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Knut","family":"Adermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinrich","family":"Sticht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,12,31]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.23.14893"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/6.1.37"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(95)00687-5"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.45.6.911"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.13.040195.000425"},{"key":"e_1_2_7_7_1","volume-title":"X\u2010PLOR Version 3.1.","author":"Br\u00fcnger A.T.","year":"1993"},{"key":"e_1_2_7_8_1","volume-title":"Protein NMR Spectroscopy.","author":"Cavanagh J.","year":"1996"},{"key":"e_1_2_7_9_1","article-title":"Identification of a novel, multifunctional \u03b2\u2010defensin (hBD\u20103) with specific antimicrobial activity: its interaction with plasma membranes of Xenopus oocytes and the induction of macrophage chemoattraction","author":"Conejo\u2010Garcia J.R.","year":"2001","journal-title":"Cell Tissue Res."},{"key":"e_1_2_7_10_1","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1096\/fj.00-0865fje","article-title":"Human \u03b2\u2010defensin 4: A novel inducible peptide with a specific salt\u2010sensitive spectrum of antimicrobial activity","volume":"15","author":"Conejo\u2010Garcia J.R.","year":"2001","journal-title":"FASEB J."},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1006\/clin.1998.4587"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0163-7258(94)00076-F"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2911(08)60145-9"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008557200"},{"key":"e_1_2_7_15_1","first-page":"189","article-title":"CLUSTAL V: Improved software for multiple sequence alignment","volume":"8","author":"Higgins D.G.","year":"1992","journal-title":"Comput. 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