6Q17

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

6Q17 の概要

• エントリーDOI: 10.2210/pdb6q17/pdb
• 分子名称: Galectin-3, methyl 3-O-[(1-beta-D-galactopyranosyl-1H-1,2,3-triazol-4-yl)methyl]-beta-D-galactopyranoside, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: sugar binding protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16266.41

構造登録者

Kishor, C.,Blanchard, H. (登録日: 2019-08-02, 公開日: 2020-04-29, 最終更新日: 2024-03-13)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.98 Å)