4PIU

CRYSTAL STRUCTURE OF BANANA LECTIN H84T MUTANT

4PIU の概要

• エントリーDOI: 10.2210/pdb4piu/pdb
• 関連するPDBエントリー: 2BMY 2BMZ 2BN0 4PIF 4PIK 4PIT
• 分子名称: Ripening-associated protein, SODIUM ION, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: jacalin-like lectin domain, lectin, sugar binding protein
• 由来する生物種: Musa acuminata (Banana)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 30577.33

構造登録者

Meagher, J.L.,Stuckey, J.A. (登録日: 2014-05-09, 公開日: 2015-11-04, 最終更新日: 2023-09-27)

主引用文献

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

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: 26496612
DOI: 10.1016/j.cell.2015.09.056

実験手法

X-RAY DIFFRACTION (1.6 Å)