4PF5

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

Summary for 4PF5

• Entry DOI: 10.2210/pdb4pf5/pdb
• Descriptor: Concanavalin-A, MANGANESE (II) ION, 4-(hydroxymethyl)-1-(alpha-D-mannopyranosyl)-1H-1,2,3-triazole, ... (5 entities in total)
• Functional Keywords: sugar binding protein, lectin, high mannose
• Biological source: Canavalia ensiformis (Jack bean)
• Total number of polymer chains: 2
• Total formula weight: 52111.12

Authors

Lafite, P.,Daniellou, R. (deposition date: 2014-04-28, release date: 2014-12-17, Last modification date: 2024-05-08)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.04 Å)