4PF5

Crystal structure of Concanavalin A complexed with a synthetic derivative of high-mannose chain

4PF5 の概要

• エントリーDOI: 10.2210/pdb4pf5/pdb
• 分子名称: Concanavalin-A, MANGANESE (II) ION, 4-(hydroxymethyl)-1-(alpha-D-mannopyranosyl)-1H-1,2,3-triazole, ... (5 entities in total)
• 機能のキーワード: sugar binding protein, lectin, high mannose
• 由来する生物種: Canavalia ensiformis (Jack bean)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 52111.12

構造登録者

Lafite, P.,Daniellou, R. (登録日: 2014-04-28, 公開日: 2014-12-17, 最終更新日: 2024-05-08)

主引用文献

Francois-Heude, M.,Mendez-Ardoy, A.,Cendret, V.,Lafite, P.,Daniellou, R.,Ortiz Mellet, C.,Garcia Fernandez, J.M.,Moreau, V.,Djedaini-Pilard, F.
Synthesis of High-Mannose Oligosaccharide Analogues through Click Chemistry: True Functional Mimics of Their Natural Counterparts Against Lectins?
Chemistry, 21:1978-1991, 2015

PubMed Abstract: Terminal "high-mannose oligosaccharides" are involved in a broad range of biological and pathological processes, from sperm-egg fusion to influenza and human immunodeficiency virus infections. In spite of many efforts, their synthesis continues to be very challenging and actually represents a major bottleneck in the field. Whereas multivalent presentation of mannopyranosyl motifs onto a variety of scaffolds has proven to be a successful way to interfere in recognition processes involving high-mannose oligosaccharides, such constructs fail at reproducing the subtle differences in affinity towards the variety of protein receptors (lectins) and antibodies susceptible to binding to the natural ligands. Here we report a family of functional high-mannose oligosaccharide mimics that reproduce not only the terminal mannopyranosyl display, but also the core structure and the branching pattern, by replacing some inner mannopyranosyl units with triazole rings. Such molecular design can be implemented by exploiting "click" ligation strategies, resulting in a substantial reduction of synthetic cost. The binding affinities of the new "click" high-mannose oligosaccharide mimics towards two mannose specific lectins, namely the plant lectin concanavalin A (ConA) and the human macrophage mannose receptor (rhMMR), have been studied by enzyme-linked lectin assays and found to follow identical trends to those observed for the natural oligosaccharide counterparts. Calorimetric determinations against ConA, and X-ray structural data support the conclusion that these compounds are not just another family of multivalent mannosides, but real "structural mimics" of the high-mannose oligosaccharides.

PubMed: 25483029
DOI: 10.1002/chem.201405481

実験手法

X-RAY DIFFRACTION (2.04 Å)