{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T13:52:12Z","timestamp":1790430732560,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2004,12,1]],"date-time":"2004-12-01T00:00:00Z","timestamp":1101859200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2004,12,1]],"date-time":"2004-12-01T00:00:00Z","timestamp":1101859200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2004,12]]},"abstract":"<jats:p>\n                    The spread of infectious diseases and the increase in antibiotic resistance represent a life\u2010threatening global development that calls for new approaches to control microorganisms. Of all potential targets, the essential and unique pathway of bacterial cell wall synthesis, targeted by the first known antibiotic penicillin, remains a perfect candidate for the development of new antibiotics. Here we show that the lantibi\u2010otic nisin exercises its antibacterial action by targeting peptidoglycan intermediates\u2019 extracellular pyrophosphate, unique to bacterial cell wall precursors. We show that nisin sequesters cell wall precursors found in the outer leaflet of bacterial plasma membranes, Lipid II and undecaprenyl pyrophosphate, into stable complexes. We propose a model of antibacterial action for nisin in which the terminal amino group of Ile1 targets the pyrophosphate groups of the bacterial cell wall precursors, where it docks via a hydrogen bond. The pyrophosphate moiety, a highly conserved chemical group different from the L\u2010Lys\u2010D\u2010Ala\u2010D\u2010Ala docking motif for vancomycin, has no biochemical analogs with comparable properties and is unlikely to be susceptible to bacterial adaptations akin to those responsible for resistance to penicillins and vancomycin.\u2014Bonev, B. B., Breukink, E., Swiezewska, E., de Kruijff, B., Watts, A. Targeting extracellular pyrophosphates underpins the high selectivity of nisin.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    18, 1862\u20101869 (2004)\n                  <\/jats:p>","DOI":"10.1096\/fj.04-2358com","type":"journal-article","created":{"date-parts":[[2004,12,2]],"date-time":"2004-12-02T14:28:25Z","timestamp":1101997705000},"page":"1862-1869","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["Targeting extracellular pyrophosphates underpins the high selectivity of nisin"],"prefix":"10.1096","volume":"18","author":[{"given":"Boyan B.","family":"Bonev","sequence":"first","affiliation":[{"name":"Biomembrane Structure Unit, Department of Biochemistry University of Oxford Oxford UK"},{"name":"School of Biomedical Sciences University of Nottingham Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eefjan","family":"Breukink","sequence":"additional","affiliation":[{"name":"Department Biochemistry of Membranes Institute of Biomembranes Utrecht University Utrecht Holland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Swiezewska","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Biophysics Polish Academy of Sciences Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"De Kruijff","sequence":"additional","affiliation":[{"name":"Department Biochemistry of Membranes Institute of Biomembranes Utrecht University Utrecht Holland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Watts","sequence":"additional","affiliation":[{"name":"Biomembrane Structure Unit, Department of Biochemistry University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,12,1]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(02)00316-X"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2003.08.004"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1016\/S0140-6736(96)11192-2","article-title":"Methicillin\u2010ressitant Staphylococcs aureus and vancomycin\u2010resistant enterococci: therapeutic realities and possibilities","volume":"349","author":"Gutmann M. M. L.","year":"1997","journal-title":"Lancet"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1039\/a804532a"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.62.1.181-203.1998"},{"key":"e_1_2_7_7_1","doi-asserted-by":"crossref","first-page":"3169","DOI":"10.1016\/S0021-9258(18)93392-2","article-title":"Biosynthesis of the peptidoglycan of bacterial cell walls: inhibition of cross\u2010linking by penicillins and cephalosporins","volume":"243","author":"Tipper D. J.","year":"1968","journal-title":"J. Biol. 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Biol. Chem."},{"key":"e_1_2_7_22_1","doi-asserted-by":"crossref","first-page":"24340","DOI":"10.1016\/S0021-9258(18)35771-5","article-title":"Engineeing dehydrated aminoacid residues in the antimicrobial peptide nisin","volume":"267","author":"Kuipers O. P.","year":"1992","journal-title":"J. Biol. Chem."},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(78)90706-6"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.18388\/abp.1994_4713"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRev.185.420"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRev.128.2042"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.470372"},{"key":"e_1_2_7_28_1","article-title":"Rotational\u2010echo double resonance","volume":"81","author":"Guillion T.","year":"1989","journal-title":"J. Magn. 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