4jfu | pdb_00004jfu

Crystal structure of a bacterial fucosidase with iminosugar inhibitor

spinqualitylabelsall models 4jfu, resolution 1.66Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4jfu is a 2 chain structure with sequence from Bactn. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL, IMD, K80, SO4 Related: 2wvv, 4j27, 4j28, 4jfs, 4jft, 4jfv, 4jfw Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Enhanced metabolism of fucose through fucosidase overexpression is a signature of some cancer types, thus suggesting that fucosidase-targetted ligands could play the role of drug-delivery vectors. Herein, we describe the synthesis of a new series of pyrrolidine-ferrocene conjugates, consisting of a L-fuco-configured dihydroxypyrrolidine as the fucosidase ligand armed with a cytotoxic ferrocenylamine moeity. Three-dimensional structures of several of these fucosidase inhibitors reveal transition-state-mimicking (3)E conformations. Elaboration with the ferrocenyl moiety results in sub-micromolar inhibitors of both bovine and bacterial fucosidases, with the 3D structure of the latter revealing electron density indicative of highly mobile alkylferrocene compounds. The best compounds show a strong antiproliferative effect, with up to 100% inhibition of the proliferation of MDA-MB-231 cancer cells at 50 muM. alpha-L-fucosidase inhibition by pyrrolidine-ferrocene hybrids: rationalization of ligand-binding properties by structural studies.,Hottin A, Wright DW, Steenackers A, Delannoy P, Dubar F, Biot C, Davies GJ, Behr JB Chemistry. 2013 Jul 15;19(29):9526-33. doi: 10.1002/chem.201301001. Epub 2013 Jun, 5. PMID:23740878 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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