Publication Type
Peer Reviewed Journal
Mandatory Citation Fields
Swanson, Michael D.; Boudreaux, Daniel M.; Salmon, Loic; Chugh, Jeetender; Winter, Harry C.; Meagher, Jennifer L.; Andre, Sabine; Murphy, Paul V.; Oscarson, Stefan; Roy, Rene; et al
2015
October
Cell
Engineering a Therapeutic Lectin by Uncoupling Mitogenicity from Antiviral Activity
Published
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Engineering a Therapeutic Lectin by Uncoupling Mitogenicity from Antiviral Activity
163
3
746
758
A 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 crystallog., NMR spectroscopy, and glycocluster assays reveal that loss of mitogenicity is strongly correlated with loss of pi-pi stacking between arom. amino acids H84 and Y83, which removes a wall sepg. 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
http://www.sciencedirect.com/science/article/pii/S0092867415012738
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