Show simple item record

dc.contributor.authorSwanson, Michael D.
dc.contributor.authorBoudreaux, Daniel M.
dc.contributor.authorSalmon, Loïc
dc.contributor.authorChugh, Jeetender
dc.contributor.authorWinter, Harry C.
dc.contributor.authorMeagher, Jennifer L.
dc.contributor.authorAndré, Sabine
dc.contributor.authorMurphy, Paul V.
dc.contributor.authorOscarson, Stefan
dc.contributor.authorRoy, René
dc.contributor.authorKing, Steven
dc.contributor.authorKaplan, Mark H.
dc.contributor.authorGoldstein, Irwin J.
dc.contributor.authorTarbet, E. Bart
dc.contributor.authorHurst, Brett L.
dc.contributor.authorSmee, Donald F.
dc.contributor.authorde la Fuente, Cynthia
dc.contributor.authorHoffmann, Hans-Heinrich
dc.contributor.authorXue, Yi
dc.contributor.authorRice, Charles M.
dc.contributor.authorSchols, Dominique
dc.contributor.authorGarcia, J. Victor
dc.contributor.authorStuckey, Jeanne A.
dc.contributor.authorGabius, Hans-Joachim
dc.contributor.authorAl-Hashimi, Hashim M.
dc.contributor.authorMarkovitz, David M.
dc.date.accessioned2018-09-20T16:26:03Z
dc.date.available2018-09-20T16:26:03Z
dc.date.issued2015-10-01
dc.identifier.citationSwanson, Michael D. Boudreaux, Daniel M.; Salmon, Loïc; Chugh, Jeetender; Winter, Harry C.; Meagher, Jennifer L.; André, Sabine; Murphy, Paul V.; Oscarson, Stefan; Roy, René; King, Steven; Kaplan, Mark H.; Goldstein, Irwin J.; Tarbet, E. Bart; Hurst, Brett L.; Smee, Donald F.; de la Fuente, Cynthia; Hoffmann, Hans-Heinrich; Xue, Yi; Rice, Charles M.; Schols, Dominique; Garcia, J. Victor; Stuckey, Jeanne A.; Gabius, Hans-Joachim; Al-Hashimi, Hashim M.; Markovitz, David M. (2015). Engineering a therapeutic lectin by uncoupling mitogenicity from antiviral activity. Cell 163 (3), 746-758
dc.identifier.issn0092-8674
dc.identifier.urihttp://hdl.handle.net/10379/14081
dc.description.abstractA key effector route of the Sugar Code involves lectins that exert crucial regulatory controls by targeting distinct cellular glycans. We demonstrate that a single amino-acid substitution in a banana lectin, replacing histidine 84 with a threonine, significantly reduces its mitogenicity, while preserving its broad-spectrum antiviral potency. X-ray crystallography, NMR spectroscopy, and glycocluster assays reveal that loss of mitogenicity is strongly correlated with loss of pi-pi stacking between aromatic amino acids H84 and Y83, which removes a wall separating two carbohydrate binding sites, thus diminishing multivalent interactions. On the other hand, monovalent interactions and antiviral activity are preserved by retaining other wild-type conformational features and possibly through unique contacts involving the T84 side chain. Through such fine-tuning, target selection and downstream effects of a lectin can be modulated so as to knock down one activity, while preserving another, thus providing tools for therapeutics and for understanding the Sugar Code.
dc.publisherElsevier BV
dc.relation.ispartofCell
dc.subjectbanana lectin
dc.subjectsugar code
dc.subjectcyanovirin-n
dc.subjectglycodendrimersomes
dc.subjectrecognition
dc.subjectspecificity
dc.subjectgalectin
dc.subjectdynamics
dc.titleEngineering a therapeutic lectin by uncoupling mitogenicity from antiviral activity
dc.typeArticle
dc.identifier.doi10.1016/j.cell.2015.09.056
dc.local.publishedsourcehttps://doi.org/10.1016/j.cell.2015.09.056
nui.item.downloads0


Files in this item

This item appears in the following Collection(s)

Show simple item record