6TF7

Human galectin-3c in complex with a galactose derivative

6TF7 の概要

• エントリーDOI: 10.2210/pdb6tf7/pdb
• 分子名称: Galectin-3, THIOCYANATE ION, CHLORIDE ION, ... (5 entities in total)
• 機能のキーワード: 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: 16446.04

構造登録者

Nilsson, U.J.,Zetterberg, F.,Hakansson, M.,Logan, D.T. (登録日: 2019-11-13, 公開日: 2020-11-18, 最終更新日: 2024-01-24)

主引用文献

Dahlqvist, A.,Mandal, S.,Peterson, K.,Hakansson, M.,Logan, D.T.,Zetterberg, F.R.,Leffler, H.,Nilsson, U.J.
3-Substituted 1-Naphthamidomethyl-C-galactosyls Interact with Two Unique Sub-sites for High-Affinity and High-Selectivity Inhibition of Galectin-3.
Molecules, 24:-, 2019

PubMed Abstract: The galectins are a family of galactose-binding proteins playing key roles in inflammatory processes and cancer. However, they are structurally very closely related, and discovery of highly selective inhibitors is challenging. In this work, we report the design of novel inhibitors binding to a subsite unique to galectin-3, which confers both high selectivity and affinity towards galectin-3. Olefin cross metathesis between allyl β-C-galactopyranosyl and 1-vinylnaphthalenes or acylation of aminomethyl β-C-galactopyranosyl with 1-naphthoic acid derivatives gave C-galactopyranosyls carrying 1-naphthamide structural elements that interacted favorably with a galectin-3 unique subsite according to molecular modeling and X-ray structural analysis of two inhibitor-galectin-3 complexes. Affinities were down to sub-µM and selectivities over galectin-1, 2, 4 -terminal domain, 4 C-terminal domain, 7, 8 -terminal domain, 9 -terminal domain, and 9 C-terminal domain were high. These results show that high affinity and selectivity for a single galectin can be achieved by targeting unique subsites, which holds promise for further development of small and selective galectin inhibitors.

PubMed: 31842451
DOI: 10.3390/molecules24244554

実験手法

X-RAY DIFFRACTION (1.4 Å)