4JCK

Galectin-3 carbohydrate recognition domain in complex with thioditaloside

4JCK の概要

• エントリーDOI: 10.2210/pdb4jck/pdb
• 関連するPDBエントリー: 4JC1
• 関連するBIRD辞書のPRD_ID: PRD_900109
• 分子名称: Galectin-3, beta-D-talopyranose-(1-1)-1-thio-beta-D-talopyranose, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: beta sandwich, carbohydrate binding protein, sugar binding protein-inhibitor complex, sugar binding protein/inhibitor
• 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: 16448.24

構造登録者

Bum-Erdene, K.,Blanchard, H. (登録日: 2013-02-22, 公開日: 2013-07-31, 最終更新日: 2024-02-28)

主引用文献

Bum-Erdene, K.,Gagarinov, I.A.,Collins, P.M.,Winger, M.,Pearson, A.G.,Wilson, J.C.,Leffler, H.,Nilsson, U.J.,Grice, I.D.,Blanchard, H.
Investigation into the feasibility of thioditaloside as a novel scaffold for galectin-3-specific inhibitors.
Chembiochem, 14:1331-1342, 2013

PubMed Abstract: Galectin-3 is extensively involved in metabolic and disease processes, such as cancer metastasis, thus giving impetus for the design of specific inhibitors targeting this β-galactose-binding protein. Thiodigalactoside (TDG) presents a scaffold for construction of galectin inhibitors, and its inhibition of galectin-1 has already demonstrated beneficial effects as an adjuvant with vaccine immunotherapy, thereby improving the survival outcome of tumour-challenged mice. A novel approach--replacing galactose with its C2 epimer, talose--offers an alternative framework, as extensions at C2 permit exploitation of a galectin-3-specific binding groove, thereby facilitating the design of selective inhibitors. We report the synthesis of thioditaloside (TDT) and crystal structures of the galectin-3 carbohydrate recognition domain in complexes with TDT and TDG. The different abilities of galactose and talose to anchor to the protein correlate with molecular dynamics studies, likely explaining the relative disaccharide binding affinities. The feasibility of a TDT scaffold to enable access to a particular galectin-3 binding groove and the need for modifications to optimise such a scaffold for use in the design of potent and selective inhibitors are assessed.

PubMed: 23864426
DOI: 10.1002/cbic.201300245

実験手法

X-RAY DIFFRACTION (1.15 Å)