8PBF

Galectin-3C in complex with a triazolesulfane derivative

8PBF の概要

• エントリーDOI: 10.2210/pdb8pbf/pdb
• 分子名称: Galectin-3, (2~{R},3~{S},4~{S},5~{R},6~{S})-2-(hydroxymethyl)-6-[(2~{S},3~{R},4~{S},5~{R},6~{R})-6-(hydroxymethyl)-3,5-bis(oxidanyl)-4-(4-phenylsulfanyl-1,2,3-triazol-1-yl)oxan-2-yl]sulfanyl-oxane-3,4,5-triol, THIOCYANATE ION, ... (4 entities in total)
• 機能のキーワード: inhibitor, complex, sugar binding protein, structure-based inhibitor design
• 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: 16276.70

構造登録者

Kumar, R.,Mahanti, M. (登録日: 2023-06-09, 公開日: 2023-11-08, 最終更新日: 2023-11-22)

主引用文献

Mahanti, M.,Pal, K.B.,Kumar, R.,Schulze, M.,Leffler, H.,Logan, D.T.,Nilsson, U.J.
Ligand Sulfur Oxidation State Progressively Alters Galectin-3-Ligand Complex Conformations To Induce Affinity-Influencing Hydrogen Bonds.
J.Med.Chem., 66:14716-14723, 2023

PubMed Abstract: Galectins play biological roles in immune regulation and tumor progression. Ligands with high affinity for the shallow, hydrophilic galectin-3 ligand binding site rely primarily on a galactose core with appended aryltriazole moieties, making hydrophobic interactions and π-stacking. We designed and synthesized phenyl sulfone, sulfoxide, and sulfide-triazolyl thiogalactoside derivatives to create affinity-enhancing hydrogen bonds, hydrophobic and π-interactions. Crystal structures and thermodynamic analyses revealed that the sulfoxide and sulfone ligands form hydrogen bonds while retaining π-interactions, resulting in improved affinities and unique binding poses. The sulfoxide, bearing one hydrogen bond acceptor, leads to an affinity decrease compared to the sulfide, whereas the corresponding sulfone forms three hydrogen bonds, two directly with Asn and Arg side chains and one water-mediated to an Asp side chain, respectively, which alters the complex structure and increases affinity. These findings highlight that the sulfur oxidation state influences both the interaction thermodynamics and structure.

PubMed: 37878264
DOI: 10.1021/acs.jmedchem.3c01223

実験手法

X-RAY DIFFRACTION (1.14 Å)