31ml | pdb_000031ml

Crystal structure of the complex of galectin-8N-Methyl 2,6-anhydro-3-deoxy-3-S-(b-D-galactopyranosyl)-3-thio-D-glycero-L-altro-heptonate

spinqualitylabelsall models 31ml, resolution 1.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 31ml is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.5Å Ligands: A1KM9, GAL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function LEG8_HUMAN Lectin with a marked preference for 3'-O-sialylated and 3'-O-sulfated glycans. Publication Abstract from PubMed Achieving isoform selectivity within the galectin family remains a central challenge in glycomimetic drug design due to the highly conserved architecture of their carbohydrate recognition domains. Here, we define the structural and thermodynamic basis of recognition of a series of C-glycosylic 1,2-thiodisaccharides targeting human galectin-7 and the N-terminal domain of galectin-8 (galectin-8N). Using an integrated approach combining fluorescence polarization, isothermal titration calorimetry, and high-resolution X-Ray crystallography, we establish a clear structure-activity relationship across the ligand series. Compound 17 emerges as the most potent galectin-8N ligand (K(d) = 13 muM), outperforming thiodigalactoside, while compound 13 shows preferential binding to galectin-7, demonstrating tunable isoform bias. Structural analysis reveals a conserved anchoring mechanism in which the beta-galactoside unit (Gly-1) drives affinity through a rigid hydrogen-bonding and pi-stacking network, whereas the second sugar (Gly-2) modulates potency by adopting distinct orientations in galectin-specific extended binding sites. Notably, ligand binding converges on conserved motifs while leaving nonconserved regions unexploited, highlighting clear opportunities for structure-guided optimization. Collectively, this work establishes C-glycosylic thiodisaccharides as a robust platform for selective galectin targeting and provides actionable design principles for next-generation inhibitors. Structural and Biophysical Characterization of C-Glycosylic 1,2-Thiodisaccharides Reveals Determinants of Selective Binding to Galectin-7 and Galectin-8N.,Tsagkarakou AS, Kantsadi AL, Theodoridou VI, Veliotis N, Lazar L, Jozsef J, Juhasz L, Kontopidis G, Leffler H, Nilsson UJ, Somsak L, Leonidas DD ChemMedChem. 2026 Aug 27;21(16):e70439. doi: 10.1002/cmdc.70439. PMID:42603778 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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