{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:59:29Z","timestamp":1790535569347,"version":"4.1.0"},"reference-count":45,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2019,2,6]],"date-time":"2019-02-06T00:00:00Z","timestamp":1549411200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005416","name":"Norwegian Research Council","doi-asserted-by":"publisher","award":["171631"],"award-info":[{"award-number":["171631"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005416","name":"Norwegian Research Council","doi-asserted-by":"publisher","award":["183613"],"award-info":[{"award-number":["183613"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005416","name":"Norwegian Research Council","doi-asserted-by":"publisher","award":["247730"],"award-info":[{"award-number":["247730"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005366","name":"Universitetet i Oslo","doi-asserted-by":"publisher","award":["financial support to J.E.H. and J.B.H."],"award-info":[{"award-number":["financial support to J.E.H. and J.B.H."]}],"id":[{"id":"10.13039\/501100005366","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diarrhea caused by enterotoxigenic Escherichia coli (ETEC) is one of the leading causes of mortality in children under five years of age and is a great burden on developing countries. The major virulence factor of the bacterium is the heat-labile enterotoxin (LT), a close homologue of the cholera toxin. The toxins bind to carbohydrate receptors in the gastrointestinal tract, leading to toxin uptake and, ultimately, to severe diarrhea. Previously, LT from human- and porcine-infecting ETEC (hLT and pLT, respectively) were shown to have different carbohydrate-binding specificities, in particular with respect to N-acetyllactosamine-terminating glycosphingolipids. Here, we probed 11 single-residue variants of the heat-labile enterotoxin with surface plasmon resonance spectroscopy and compared the data to the parent toxins. In addition we present a 1.45 \u00c5 crystal structure of pLTB in complex with branched lacto-N-neohexaose (Gal\u03b24GlcNAc\u03b26[Gal\u03b24GlcNAc\u03b23]Gal\u03b24Glc). The largest difference in binding specificity is caused by mutation of residue 94, which links the primary and secondary binding sites of the toxins. Residue 95 (and to a smaller extent also residues 7 and 18) also contribute, whereas residue 4 shows no effect on monovalent binding of the ligand and may rather be important for multivalent binding and avidity.<\/jats:p>","DOI":"10.3390\/ijms20030703","type":"journal-article","created":{"date-parts":[[2019,2,6]],"date-time":"2019-02-06T11:51:12Z","timestamp":1549453872000},"page":"703","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Specificity of Escherichia coli Heat-Labile Enterotoxin Investigated by Single-Site Mutagenesis and Crystallography"],"prefix":"10.3390","volume":"20","author":[{"given":"Julie Elisabeth","family":"Heggelund","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Oslo, Postbox 1033 Blindern, 0315 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel Benjamin","family":"Heim","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Oslo, Postbox 1033 Blindern, 0315 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregor","family":"Bajc","sequence":"additional","affiliation":[{"name":"Department of Biology, Biotechnical Faculty, University of Ljubljana, Jamnikarjeva 101, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vesna","family":"Hodnik","sequence":"additional","affiliation":[{"name":"Department of Biology, Biotechnical Faculty, University of Ljubljana, Jamnikarjeva 101, 1000 Ljubljana, Slovenia"},{"name":"Department of Molecular Biology and Nanobiotechnology, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana; Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9916-8465","authenticated-orcid":false,"given":"Gregor","family":"Anderluh","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Nanobiotechnology, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana; Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6688-8151","authenticated-orcid":false,"given":"Ute","family":"Krengel","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Oslo, Postbox 1033 Blindern, 0315 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1016\/S1473-3099(18)30475-4","article-title":"Morbidity and mortality due to shigella and enterotoxigenic Escherichia coli diarrhoea: The Global Burden of Disease Study 1990\u20132016","volume":"11","author":"Khalil","year":"2018","journal-title":"Lancet Infect. 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