9FYJ
N-terminal domain of human galectin-8 in complex with an alpha-galactoside ligand
This is a non-PDB format compatible entry.
Summary for 9FYJ
| Entry DOI | 10.2210/pdb9fyj/pdb |
| Descriptor | Isoform 1 of Galectin-8, 2-[[(2~{R},3~{R},4~{S},5~{S},6~{R})-2-(3,4-dichlorophenyl)sulfanyl-6-(hydroxymethyl)-5-oxidanyl-3-prop-2-ynoxy-oxan-4-yl]oxymethyl]-3-methyl-benzimidazole-5-carboxylic acid, CHLORIDE ION, ... (4 entities in total) |
| Functional Keywords | inhibitor, complex, drug design, sugar binding protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 35733.94 |
| Authors | Adrover Forteza, J.,Puric, E.,Nilsson, U.J.,Anderluh, M.,Logan, D.T. (deposition date: 2024-07-03, release date: 2025-03-12) |
| Primary citation | Puric, E.,Hassan, M.,Sjovall, F.,Tomasic, T.,Pevec, M.,Lah, J.,Forteza, J.A.,Sundin, A.,Leffler, H.,Nilsson, U.J.,Logan, D.T.,Anderluh, M. Nanomolar inhibitor of the galectin-8 N-terminal domain binds via a non-canonical cation-pi interaction. Commun Chem, 8:59-59, 2025 Cited by PubMed Abstract: Galectin-8 is a tandem-repeat galectin consisting of two distinct carbohydrate recognition domains and is a potential drug target. We have developed a library of galectin-8N inhibitors that exhibit high nanomolar K values as determined by a competitive fluorescence polarization assay. A detailed thermodynamic analysis of the binding of D-galactosides to galectin-8N by isothermal titration calorimetry reveals important differences in enthalpic and/or entropic contributions to binding. Contrary to expectations, the binding of 2-O-propargyl-D-galactoside was found to strongly increase the binding enthalpy, whereas the binding of 2-O-carboxymethylene-D-galactoside was surprisingly less enthalpy-driven. The results of our work suggest that the ethynyl group can successfully replace the carboxylate group when targeting the water-exposed guanidine moiety of a critical arginine residue. This results in only a minor loss of affinity and an adjusted enthalpic contribution to the overall binding due to non-canonical cation-π interactions, as evidenced by the obtained crystal structure of 2-O-propargyl-D-galactoside in complex with the N-terminal domain of galectin-8. Such an interaction has neither been identified nor discussed to date in a small-molecule ligand-protein complex. PubMed: 39994474DOI: 10.1038/s42004-025-01458-6 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.08 Å) |
Structure validation
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