8pbf

Galectin-3C in complex with a triazolesulfane derivative

spinqualitylabelsall models 8pbf, resolution 1.14Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8pbf is a 1 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 1.14Å Ligands: SCN, Y58 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function LEG3_HUMAN Galactose-specific lectin which binds IgE. May mediate with the alpha-3, beta-1 integrin the stimulation by CSPG4 of endothelial cells migration. Together with DMBT1, required for terminal differentiation of columnar epithelial cells during early embryogenesis (By similarity). In the nucleus: acts as a pre-mRNA splicing factor. Involved in acute inflammatory responses including neutrophil activation and adhesion, chemoattraction of monocytes macrophages, opsonization of apoptotic neutrophils, and activation of mast cells. Publication Abstract from PubMed Galectins play biological roles in immune regulation and tumor progression. Ligands with high affinity for the shallow, hydrophilic galectin-3 ligand binding site rely primarily on a galactose core with appended aryltriazole moieties, making hydrophobic interactions and pi-stacking. We designed and synthesized phenyl sulfone, sulfoxide, and sulfide-triazolyl thiogalactoside derivatives to create affinity-enhancing hydrogen bonds, hydrophobic and pi-interactions. Crystal structures and thermodynamic analyses revealed that the sulfoxide and sulfone ligands form hydrogen bonds while retaining pi-interactions, resulting in improved affinities and unique binding poses. The sulfoxide, bearing one hydrogen bond acceptor, leads to an affinity decrease compared to the sulfide, whereas the corresponding sulfone forms three hydrogen bonds, two directly with Asn and Arg side chains and one water-mediated to an Asp side chain, respectively, which alters the complex structure and increases affinity. These findings highlight that the sulfur oxidation state influences both the interaction thermodynamics and structure. Ligand Sulfur Oxidation State Progressively Alters Galectin-3-Ligand Complex Conformations To Induce Affinity-Influencing Hydrogen Bonds.,Mahanti M, Pal KB, Kumar R, Schulze M, Leffler H, Logan DT, Nilsson UJ J Med Chem. 2023 Oct 25. doi: 10.1021/acs.jmedchem.3c01223. PMID:37878264 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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