Peer-Reviewed Journal Details
Mandatory Fields
Swanson MD, Boudreaux DM;Salmon L;Chugh J;Winter HC;Meagher JL;Andr┐┐ S;Murphy PV;Oscarson S;Roy R;King S;Kaplan MH;Goldstein IJ;Tarbet EB;Hurst BL;Smee DF;de la Fuente C;Hoffmann HH;Xue Y;Rice CM;Schols D;Garcia JV;Stuckey JA;Gabius HJ;Al-Hashimi HM;Markovitz DM
Engineering a Therapeutic Lectin by Uncoupling Mitogenicity from Antiviral Activity.
Altmetric: 72WOS: 31 ()
Optional Fields
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 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..
Grant Details
Publication Themes