6QLR

Galectin-3C in complex with fluoroaryltriazole monothiogalactoside derivative 5

Summary for 6QLR

• Entry DOI: 10.2210/pdb6qlr/pdb
• Descriptor: Galectin-3, (2~{R},3~{R},4~{S},5~{R},6~{S})-4-[4-[3,5-bis(fluoranyl)phenyl]-1,2,3-triazol-1-yl]-2-(hydroxymethyl)-6-(4-methylphenyl)sulfanyl-oxane-3,5-diol, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: lectin, carbohydrate-binding protein, galactose-specific lectin 3, galactoside-binding protein, galbp, ige-6 binding protein, l-31, laminin-binding protein, lectin l-29, mac-2, sugar binding protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 16185.97

Authors

Kumar, R.,Peterson, K.,Nilsson, U.J.,Logan, D.T. (deposition date: 2019-02-01, release date: 2019-07-10, Last modification date: 2024-05-15)

Primary citation

Kumar, R.,Ignjatovic, M.M.,Peterson, K.,Olsson, M.,Leffler, H.,Ryde, U.,Nilsson, U.J.,Logan, D.T.
Structure and Energetics of Ligand-Fluorine Interactions with Galectin-3 Backbone and Side-Chain Amides: Insight into Solvation Effects and Multipolar Interactions.
Chemmedchem, 14:1528-1536, 2019

PubMed Abstract: Multipolar fluorine-amide interactions with backbone and side-chain amides have been described as important for protein-ligand interactions and have been used to improve the potency of synthetic inhibitors. In this study, fluorine interactions within a well-defined binding pocket on galectin-3 were investigated systematically using phenyltriazolyl-thiogalactosides fluorinated singly or multiply at various positions on the phenyl ring. X-ray structures of the C-terminal domain of galectin-3 in complex with eight of these ligands revealed potential orthogonal fluorine-amide interactions with backbone amides and one with a side-chain amide. The two interactions involving main-chain amides seem to have a strong influence on affinity as determined by fluorescence anisotropy. In contrast, the interaction with the side-chain amide did not influence affinity. Quantum mechanics calculations were used to analyze the relative contributions of these interactions to the binding energies. No clear correlation could be found between the relative energies of the fluorine-main-chain amide interactions and the overall binding energy. Instead, dispersion and desolvation effects play a larger role. The results confirm that the contribution of fluorine-amide interactions to protein-ligand interactions cannot simply be predicted, on geometrical considerations alone, but require careful consideration of the energetic components.

PubMed: 31246331
DOI: 10.1002/cmdc.201900293

Experimental method

X-RAY DIFFRACTION (0.97 Å)