6G0V

Human Galectin-3 in complex with a TF tumor-associated antigen mimetic

Summary for 6G0V

• Entry DOI: 10.2210/pdb6g0v/pdb
• Descriptor: Galectin-3, (3~{R},5~{R},6~{S},7~{S},8~{R},13~{S})-5-(hydroxymethyl)-7-[(2~{S},3~{R},4~{S},5~{R},6~{R})-6-(hydroxymethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]oxy-6-oxidanyl-11-oxidanylidene-2,4-dioxa-9-thia-12-azatricyclo[8.4.0.0^{3,8}]tetradec-1(10)-ene-13-carboxylic acid, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: galectin-3, thomsen-friedenreich, tumour antigen, cancer, tf-mimetic, cell adhesion
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 16266.04

Authors

Trovao, F.G.,Santarsia, S.,Carvalho, A.L. (deposition date: 2018-03-19, release date: 2018-08-22, Last modification date: 2024-05-08)

Primary citation

Santarsia, S.,Grosso, A.S.,Trovao, F.,Jimenez-Barbero, J.,Carvalho, A.L.,Nativi, C.,Marcelo, F.
Molecular Recognition of a Thomsen-Friedenreich Antigen Mimetic Targeting Human Galectin-3.
ChemMedChem, 13:2030-2036, 2018

PubMed Abstract: Overexpression of the Thomsen-Friedenreich (TF) antigen in cell membrane proteins occurs in 90 % of adenocarcinomas. Additionally, the binding of the TF antigen to human galectin-3 (Gal-3), also frequently overexpressed in malignancy, promotes cancer progression and metastasis. In this context, structures that interfere with this specific interaction have the potential to prevent cancer metastasis. A multidisciplinary approach combining the optimized synthesis of a TF antigen mimetic with NMR, X-ray crystallography methods, and isothermal titration calorimetry assays was used to unravel the molecular structural details that govern the Gal-3/TF mimetic interaction. The TF mimetic has a binding affinity for Gal-3 similar to that of the TF natural antigen and retains the binding epitope and bioactive conformation observed for the native antigen. Furthermore, from a thermodynamic perspective, a decrease in the enthalpic contribution was observed for the Gal-3/TF mimetic complex; however, this behavior is compensated by a favorable gain in entropy. From a structural perspective, these results establish our TF mimetic as a scaffold to design multivalent solutions to potentially interfere with Gal-3 aberrant interactions and for likely use in hampering Gal-3-mediated cancer cell adhesion and metastasis.

PubMed: 30094951
DOI: 10.1002/cmdc.201800525

Experimental method

X-RAY DIFFRACTION (1.09 Å)