4PIT
Crystal Structure of Banana Lectin H84T bound to dimannose
Summary for 4PIT
| Entry DOI | 10.2210/pdb4pit/pdb |
| Related | 4PIF 4PIK 4PIU |
| Related PRD ID | PRD_900111 |
| Descriptor | Ripening-associated protein, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose, alpha-D-mannopyranose, ... (5 entities in total) |
| Functional Keywords | lectin, sugar binding protein |
| Biological source | Musa acuminata (Banana) |
| Total number of polymer chains | 4 |
| Total formula weight | 65066.42 |
| Authors | Meagher, J.L.,Stuckey, J.A. (deposition date: 2014-05-09, release date: 2015-11-04, Last modification date: 2023-12-27) |
| Primary citation | Swanson, M.D.,Boudreaux, D.M.,Salmon, L.,Chugh, J.,Winter, H.C.,Meagher, J.L.,Andre, S.,Murphy, P.V.,Oscarson, S.,Roy, R.,King, S.,Kaplan, M.H.,Goldstein, I.J.,Tarbet, E.B.,Hurst, B.L.,Smee, D.F.,de la Fuente, C.,Hoffmann, H.H.,Xue, Y.,Rice, C.M.,Schols, D.,Garcia, J.V.,Stuckey, J.A.,Gabius, H.J.,Al-Hashimi, H.M.,Markovitz, D.M. Engineering a Therapeutic Lectin by Uncoupling Mitogenicity from Antiviral Activity. Cell, 163:746-758, 2015 Cited by PubMed Abstract: 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. PubMed: 26496612DOI: 10.1016/j.cell.2015.09.056 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.55 Å) |
Structure validation
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