3T2T

Crystal structure of human galectin-1 in complex with methyl 2-O-acetyl-3-O-toluoyl-beta-D-talopyranoside

Summary for 3T2T

• Entry DOI: 10.2210/pdb3t2t/pdb
• Related: 3TIL 3TIM
• Descriptor: Galectin-1, methyl 2-O-acetyl-3-O-(4-methylbenzoyl)-beta-D-talopyranoside (3 entities in total)
• Functional Keywords: beta sandwich, lectin, sugar binding protein-inhibitor complex, sugar binding protein/inhibitor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 30272.41

Authors

Blanchard, H.,Collins, P.M. (deposition date: 2011-07-23, release date: 2011-12-28, Last modification date: 2020-07-29)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.9 Å)