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4JC1

Galectin-3 carbohydrate recognition domain in complex with thiodigalactoside

Summary for 4JC1
Entry DOI10.2210/pdb4jc1/pdb
Related4JCK
Related PRD IDPRD_900027
DescriptorGalectin-3, beta-D-galactopyranose-(1-1)-1-thio-beta-D-galactopyranose, CHLORIDE ION, ... (4 entities in total)
Functional Keywordsbeta sandwich, carbohydrate binding protein, sugar binding protein
Biological sourceHomo sapiens (human)
Total number of polymer chains1
Total formula weight16590.05
Authors
Collins, P.M.,Blanchard, H. (deposition date: 2013-02-21, release date: 2013-07-31, Last modification date: 2023-09-20)
Primary citationBum-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
Cited by
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
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.5 Å)
Structure validation

238582

数据于2025-07-09公开中

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