3T1M

Crystal structure of human galectin-3 carbohydrate recognition domain in complex with methyl 3-deoxy-2-O-toluoyl-3-N-toluoyl-beta-D-talopyranoside

3T1M の概要

• エントリーDOI: 10.2210/pdb3t1m/pdb
• 関連するPDBエントリー: 3T1L 3T2T
• 分子名称: Galectin-3, CHLORIDE ION, methyl 3-deoxy-2-O-(4-methylbenzoyl)-3-[(4-methylbenzoyl)amino]-beta-D-talopyranoside, ... (4 entities in total)
• 機能のキーワード: beta sandwich, sugar binding protein-inhibitor complex, sugar binding protein/inhibitor
• 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: 16519.34

構造登録者

Blanchard, H.,Collins, P.M. (登録日: 2011-07-22, 公開日: 2011-12-28, 最終更新日: 2024-03-20)

主引用文献

Collins, P.M.,Oberg, C.T.,Leffler, H.,Nilsson, U.J.,Blanchard, H.
Taloside inhibitors of galectin-1 and galectin-3
Chem.Biol.Drug Des., 79:339-346, 2012

PubMed Abstract: Galectin-1 and galectin-3 have roles in cancer and inflammation. Galectin-1 has recently emerged as a significant protein produced by tumour cells to promote tumour development, angiogenesis and metastasis and consequently represents an important target to inhibit. The design of inhibitors targeting the carbohydrate recognition domain that is known to recognize galactose is an important approach in the fight against cancer. Based on the analysis of crystal structures, we pursued the concept that if the galactose was replaced with talose (the C2 epimer of galactose) as a scaffold, then O2 substituents would be directed closer to the protein surface and provide opportunity to design inhibitors that are more specific towards particular galectins. Our elucidation of X-ray crystal structures of two of our synthesized talosides in complex with galectin-1 and galectin-3 provides the first atomic information on the interactions of galectins, and indeed any protein, with talosides. These results have enabled a structure-based rationale for the specificity differences shown by galectin-1 and galectin-3 towards these talosides and demonstrate new opportunities for further exploitation as specific inhibitors of galectins.

PubMed: 22136701
DOI: 10.1111/j.1747-0285.2011.01283.x

実験手法

X-RAY DIFFRACTION (1.55 Å)