5EXO

Crystal structure of Human galectin-3 CRD in complex with methyl 2-O-acetyl-3-O-(2H-chromene-3-yl-methyl)-a-D-galactopyranoside inhibitor

Summary for 5EXO

• Entry DOI: 10.2210/pdb5exo/pdb
• Descriptor: Galectin-3, CHLORIDE ION, [(2~{S},3~{R},4~{S},5~{S},6~{R})-6-(hydroxymethyl)-2-methoxy-5-oxidanyl-4-[(2-oxidanylidenechromen-3-yl)methoxy]oxan-3-yl] ethanoate, ... (4 entities in total)
• Functional Keywords: carbohydrate-recognition, beta sandwich, carbohydrate binding protein, sugar binding protein, inhibitor, coumaryl
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm: P17931
• Total number of polymer chains: 1
• Total formula weight: 16187.93

Authors

Collins, P.M.,Blanchard, H. (deposition date: 2015-11-23, release date: 2016-10-05, Last modification date: 2023-09-27)

Primary citation

Rajput, V.K.,MacKinnon, A.,Mandal, S.,Collins, P.,Blanchard, H.,Leffler, H.,Sethi, T.,Schambye, H.,Mukhopadhyay, B.,Nilsson, U.J.
A Selective Galactose-Coumarin-Derived Galectin-3 Inhibitor Demonstrates Involvement of Galectin-3-glycan Interactions in a Pulmonary Fibrosis Model.
J.Med.Chem., 59:8141-8147, 2016

PubMed Abstract: Synthesis of doubly 3-O-coumarylmethyl-substituted thiodigalactosides from bis-3-O-propargyl-thiodigalactoside resulted in highly selective and high affinity galectin-3 inhibitors. Mutant studies, structural analysis, and molecular modeling revealed that the coumaryl substituents stack onto arginine side chains. One inhibitor displayed efficacy in a murine model of bleomycin-induced lung fibrosis similar to that of a known nonselective galectin-1/galectin-3 inhibitor, which strongly suggests that blocking galectin-3 glycan recognition is an important antifibrotic drug target.

PubMed: 27500311
DOI: 10.1021/acs.jmedchem.6b00957

Experimental method

X-RAY DIFFRACTION (1.502 Å)