4y24

Complex of human Galectin-1 and TD-139Complex of human Galectin-1 and TD-139

Structural highlights 4y24 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: Related: 4y1v, 4y1z, 4y1y, 4y1u, 4y1x, 4y22, 4y20 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [LEG1_HUMAN] May regulate apoptosis, cell proliferation and cell differentiation. Binds beta-galactoside and a wide array of complex carbohydrates. Inhibits CD45 protein phosphatase activity and therefore the dephosphorylation of Lyn kinase. Publication Abstract from PubMed Human galectins are promising targets for cancer immunotherapeutic and fibrotic disease-related drugs. We report herein the binding interactions of three thio-digalactosides (TDGs) including TDG itself, TD139 (3,3'-deoxy-3,3'-bis-(4-[m-fluorophenyl]-1H-1,2,3-triazol-1-yl)-thio-digalactosid e, recently approved for the treatment of idiopathic pulmonary fibrosis), and TAZTDG (3-deoxy-3-(4-[m-fluorophenyl]-1H-1,2,3-triazol-1-yl)-thio-digalactoside) with human galectins-1, -3 and -7 as assessed by X-ray crystallography, isothermal titration calorimetry and NMR spectroscopy. Five binding subsites (A-E) make up the carbohydrate-recognition domains of these galectins. We identified novel interactions between an arginine within subsite E of the galectins and an arene group in the ligands. In addition to the interactions contributed by the galactosyl sugar residues bound at subsites C and D, the fluorophenyl group of TAZTDG preferentially bound to subsite B in galectin-3, whereas the same group favored binding at subsite E in galectins-1 and -7. The characterised dual binding modes demonstrate how binding potency, reported as decreased Kd values of the TDG inhibitors from muM to nM, is improved and also offer insights to development of selective inhibitors for individual galectins. Dual thio-digalactoside-binding modes of human galectins as the structural basis for the design of potent and selective inhibitors.,Hsieh TJ, Lin HY, Tu Z, Lin TC, Wu SC, Tseng YY, Liu FT, Hsu ST, Lin CH Sci Rep. 2016 Jul 15;6:29457. doi: 10.1038/srep29457. PMID:27416897 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 4y24, resolution 2.32Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image