6TF6
Human galectin-3c in complex with a galactose derivative
Summary for 6TF6
Entry DOI | 10.2210/pdb6tf6/pdb |
Descriptor | Galectin-3, CHLORIDE ION, ~{N}-[[(2~{S},3~{S},4~{R},5~{S},6~{R})-4-[[5,6-bis(fluoranyl)-2-oxidanylidene-chromen-3-yl]methoxy]-6-(hydroxymethyl)-3,5-bis(oxidanyl)oxan-2-yl]methyl]-4-fluoranyl-naphthalene-1-carboxamide, ... (4 entities in total) |
Functional Keywords | sugar binding protein |
Biological source | Homo sapiens (Human) |
Total number of polymer chains | 1 |
Total formula weight | 16365.52 |
Authors | Nilsson, U.J.,Zetterberg, F.,Hakansson, M.,Logan, D.T. (deposition date: 2019-11-13, release date: 2020-11-18, Last modification date: 2024-01-24) |
Primary citation | 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 Cited by 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: 31842451DOI: 10.3390/molecules24244554 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.5 Å) |
Structure validation
Download full validation report