6QLP

Galectin-3C in complex with substituted polyfluoroaryl monothiogalactoside derivative 3

6QLP の概要

• エントリーDOI: 10.2210/pdb6qlp/pdb
• 分子名称: Galectin-3, TRIETHYLENE GLYCOL, (2~{R},3~{R},4~{S},5~{R},6~{S})-2-(hydroxymethyl)-6-(4-methylphenyl)sulfanyl-4-[4-[3,4,5-tris(fluoranyl)phenyl]-1,2,3-triazol-1-yl]oxane-3,5-diol, ... (5 entities in total)
• 機能のキーワード: 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
• 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: 16354.14

構造登録者

Kumar, R.,Peterson, K.,Nilsson, U.J.,Logan, D.T. (登録日: 2019-02-01, 公開日: 2019-07-10, 最終更新日: 2024-01-24)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.081 Å)