6Q0Q

Crystal structure of Human galectin-3 CRD in complex with Methyl 3-O-(1-{3-O-[1-(b-D-galactopyranosyl)-1,2,3-triazol-4-yl]-methyl-b-D-galactopyranosyl}-1,2,3-triazol-4-yl)-methyl-b-D-galactopyranoside

Summary for 6Q0Q

• Entry DOI: 10.2210/pdb6q0q/pdb
• Descriptor: Galectin-3, CHLORIDE ION, (2~{R},3~{R},4~{S},5~{R},6~{R})-2-(hydroxymethyl)-6-[4-[[(2~{R},3~{S},4~{S},5~{R},6~{R})-2-(hydroxymethyl)-6-[4-[[(2~{R},3~{S},4~{S},5~{R},6~{R})-2-(hydroxymethyl)-6-methoxy-3,5-bis(oxidanyl)oxan-4-yl]oxymethyl]-1,2,3-triazol-1-yl]-3,5-bis(oxidanyl)oxan-4-yl]oxymethyl]-1,2,3-triazol-1-yl]oxane-3,4,5-triol, ... (4 entities in total)
• Functional Keywords: sugar binding protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 16474.17

Authors

Kishor, C.,Blanchard, H. (deposition date: 2019-08-02, release date: 2020-04-29, Last modification date: 2024-03-13)

Primary citation

Dussouy, C.,Kishor, C.,Lambert, A.,Lamoureux, C.,Blanchard, H.,Grandjean, C.
Linear triazole-linked pseudo oligogalactosides as scaffolds for galectin inhibitor development.
Chem.Biol.Drug Des., 96:1123-1133, 2020

PubMed Abstract: Galectins play key roles in numerous biological processes. Their mode of action depends on their localization which can be extracellular, cytoplasmic, or nuclear and is partly mediated through interactions with β-galactose containing glycans. Galectins have emerged as novel therapeutic targets notably for the treatment of inflammatory disorders and cancers. This has stimulated the design of carbohydrate-based inhibitors targeting the carbohydrate recognition domains (CRDs) of the galectins. Pursuing this approach, we reasoned that linear oligogalactosides obtained by straightforward iterative click chemistry could mimic poly-lactosamine motifs expressed at eukaryote cell surfaces which the extracellular form of galectin-3, a prominent member of the galectin family, specifically recognizes. Affinities toward galectin-3 consistently increased with the length of the representative oligogalactosides but without reaching that of oligo-lactosamines. Elucidation of the X-ray crystal structures of the galectin-3 CRD in complex with a synthesized di- and tri-galactoside confirmed that the compounds bind within the carbohydrate-binding site. The atomic structures revealed that binding interactions mainly occur with the galactose moiety at the non-reducing end, primarily with subsites C and D of the CRD, differing from oligo-lactosamine which bind more consistently across the whole groove formed by the five subsites (A-E) of the galectin-3 CRD.

PubMed: 32220037
DOI: 10.1111/cbdd.13683

Experimental method

X-RAY DIFFRACTION (1.98601176315 Å)