5H9R

Crystal Structure of Human Galectin-3 CRD in Complex with TAZTDG

5H9R の概要

• エントリーDOI: 10.2210/pdb5h9r/pdb
• 関連するPDBエントリー: 4XBN 5H9P 5H9Q 5H9S
• 分子名称: Galectin-3, (2~{S},3~{R},4~{S},5~{R},6~{R})-2-[(2~{S},3~{R},4~{S},5~{R},6~{R})-4-[4-(3-fluorophenyl)-1,2,3-triazol-1-yl]-6-(hydroxymethyl)-3,5-bis(oxidanyl)oxan-2-yl]sulfanyl-6-(hydroxymethyl)oxane-3,4,5-triol (3 entities in total)
• 機能のキーワード: galectin, thio-digalactoside (tdg), pi-arginine interaction, fluorine bonding, sugar binding protein
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm: P17931
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18375.92

構造登録者

Hsieh, T.J.,Lin, H.Y.,Lin, C.H. (登録日: 2015-12-29, 公開日: 2016-06-29, 最終更新日: 2023-11-08)

主引用文献

Hsieh, T.J.,Lin, H.Y.,Tu, Z.,Lin, T.C.,Wu, S.C.,Tseng, Y.Y.,Liu, F.T.,Danny Hsu, S.T.,Lin, C.H.
Dual thio-digalactoside-binding modes of human galectins as the structural basis for the design of potent and selective inhibitors
Sci Rep, 6:29457-29457, 2016

PubMed Abstract: Human galectins are promising targets for cancer immunotherapeutic and fibrotic disease-related drugs. We report herein the binding interactions of three thio-digalactosides (TDGs) including TDG itself, TD139 (3,3'-deoxy-3,3'-bis-(4-[m-fluorophenyl]-1H-1,2,3-triazol-1-yl)-thio-digalactoside, recently approved for the treatment of idiopathic pulmonary fibrosis), and TAZTDG (3-deoxy-3-(4-[m-fluorophenyl]-1H-1,2,3-triazol-1-yl)-thio-digalactoside) with human galectins-1, -3 and -7 as assessed by X-ray crystallography, isothermal titration calorimetry and NMR spectroscopy. Five binding subsites (A-E) make up the carbohydrate-recognition domains of these galectins. We identified novel interactions between an arginine within subsite E of the galectins and an arene group in the ligands. In addition to the interactions contributed by the galactosyl sugar residues bound at subsites C and D, the fluorophenyl group of TAZTDG preferentially bound to subsite B in galectin-3, whereas the same group favored binding at subsite E in galectins-1 and -7. The characterised dual binding modes demonstrate how binding potency, reported as decreased Kd values of the TDG inhibitors from μM to nM, is improved and also offer insights to development of selective inhibitors for individual galectins.

PubMed: 27416897
DOI: 10.1038/srep29457

実験手法

X-RAY DIFFRACTION (1.58 Å)